Functions of angiotensin in the human body. Clinical Pharmacology - Angiotensin II synthesis inhibitors and others for arterial hypertension What is angiotensin 1 and 2

Among the main factors in the development of ischemic disease and strokes as the main causes of mortality in Russia is hypertension, which is characterized by increases in blood pressure above 140/80 mm Hg. Treatment of arterial hypertension is a long, often lifelong process. In this situation, a competent approach to the choice of antihypertensive therapy is required, characterized by significant antihypertensive efficacy, a positive effect on organs exposed to the detrimental effects of high blood pressure, minimal side effects and convenient methods of application. According to current recommendations, one of the main groups of drugs used in the treatment of arterial hypertension is angiotensin receptor 2 blockers as a single drug or in combination with other drugs.

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Mechanism of action and pharmacological effects

Angiotensin II receptor blockers (sartans) are a class of antihypertensive drugs, the mechanism of action of which is based on inhibition of the activity of the renin-angiotensin-aldosterone system (RAAS) - the main hormonal regulator of blood pressure (BP) and blood volume in the body.

ARBs inhibit (inhibit) type 1 angiotensin receptors, through which the negative effects of angiotensin II are carried out, namely:

• increased blood pressure due to vasoconstriction;
• increased reuptake of Na + ions in the kidney tubules;
• increased production of aldosterone, adrenaline and renin - the main vasoconstrictor hormones;
• stimulation of structural changes in the vascular wall and heart muscle;
• activation of the activity of the sympathetic (excitatory) nervous system.

Excessive activity of angiotensin 2 receptors leads to the appearance of harmful, often life-threatening changes in internal organs (Table 1).

Activity of type 1 receptors of angiotensin 2 in relation to internal organs:

ARBs, selectively acting on type 1 receptors, reduce vascular tone, improve diastolic function of the myocardium, stimulate a decrease in cardiac muscle hypertrophy, and reduce the secretion of hormones aldosterone, norepinephrine, endothelin. ARBs are similar in their properties to the activity of another class of antihypertensive drugs - angiotensin-converting enzyme (ACE) inhibitors: both drugs significantly improve kidney function. A switch from angiotensin II blockers to ACE inhibitors is recommended if the former cause coughing.



Metabolic effects and classification

Angiotensin receptor blockers, especially Losartan, have a uricosuric (promoting the excretion of uric acid in the urine) effect. This property provides additional benefits of combination therapy with thiazide diuretics. Most drugs on the ARB list can increase the insulin sensitivity of peripheral tissues. This effect is due to sympatholytic action, improved endothelial function and expansion of peripheral vessels.

ARBs have also been shown to act on specific PPRAγ receptors, which directly increase insulin sensitivity at the cell level and stimulate an anti-inflammatory response, reduce triglycerides and free fatty acids. Modern research has demonstrated the possibility of preventing the development of type 2 diabetes when taking ARBs.

ARB classification:



Clinical pharmacology

All drugs are highly active in the blood, have good bioavailability and have a long-term effect when taken orally, so it is recommended to take them once a day. ARBs are preferentially excreted by the liver and to a lesser extent by the kidneys, which makes it possible to use them carefully in renal failure. Because ARBs are similar in activity to ACE inhibitors, angiotensin II blockers should not be prescribed for stenosis of both renal arteries. Eprosartan and Telmisartan are relatively contraindicated in liver and bile duct diseases, since more than 90% of their concentration is eliminated by the liver. The clinical pharmacology of the master list of drugs is presented in Table 3.

Pharmacokinetic parameters of angiotensin II receptor antagonists:



ARBs affect neurohumoral interactions in the body, including the main regulatory systems: the RAAS and the sympathoadrenal system (SAS), which are responsible for the increase in blood pressure, the appearance and progression of cardiovascular pathologies.



Indications and contraindications

The main indications for the appointment of angiotensin receptor blockers:

• arterial hypertension;
• chronic heart failure (CHF functional classes II – IV according to the classification of the New York Heart Association NYHA in combinations of drugs, if it is impossible to use or ineffective ACE inhibitors) in complex treatment;
• an increase in the percentage of patients who have had acute myocardial infarction complicated by left ventricular failure and / or left ventricular systolic dysfunction, with stable hemodynamics;
• reducing the likelihood of developing acute disorders of cerebral circulation (strokes) in patients with arterial hypertension and left ventricular hypertrophy;
• nephroprotective function in patients with type 2 diabetes mellitus associated with proteinuria in order to reduce it, regress renal pathology, reduce the risk of progression of chronic renal failure to the terminal stage (prevention of hemodialysis, the likelihood of an increase in serum creatinine concentration).

Contraindications to the use of ARBs: individual intolerance, bilateral renal artery stenosis or stenosis of an artery of a single kidney, pregnancy, lactation.



Side effects

Research has shown that ARBs have the lowest reported side effects. Unlike a similar class of antihypertensive drugs, ACE inhibitors, angiotensin II receptor blockers are significantly less likely to cause coughing. With increasing dosages and in combination with taking diuretics, hypersensitivity reactions, orthostatic hypotension may develop.

In the case of ARB administration in patients with chronic renal failure or undiagnosed renal artery stenosis, hyperkalemia, an increase in creatinine and blood urea may develop, which requires a decrease in the dosage of the drug. Numerous studies have not revealed data on an increased risk of developing cancer with long-term use of angiotensin receptor blockers.

Pharmacological interactions

Angiotensin II receptor blockers can enter into pharmacodynamic interactions, changing the manifestation of the hypotensive effect, increasing the concentration of potassium in the blood serum when combined with potassium-sparing diuretics and potassium-sparing drugs. Pharmacokinetic interactions are also possible with Warfarin and Digoxin (Table 4).

Drug interactions with angiotensin II receptor blockers:

Interacting drug	Angiotensin II receptor antagonists	Interaction result
Alcohol	Losartan, Valsartan, Eprosartan
Antihypertensive drugs, diuretics	Everything	Strengthening the hypotensive effect
Non-steroidal anti-inflammatory drugs, estrogens, sympathomimetics	Everything	Weakening of the hypotensive effect
Potassium-sparing diuretics, potassium-containing drugs	Everything	Hyperkalemia
Warfarin	Valsartan, Telmesartan	Decrease in maximum blood concentration, increase in prothrombin time
Digoxin	Telmisartan	Increase in maximum blood concentration

List of drugs and their trade names

Currently, in a market economy, there are a significant number of brands of drugs containing the same active ingredient. To select a suitable drug, it is imperative to consult a specialist.



A list of the most appointed ARBs and their trade names:

Active substance	Trade names (manufacturing company)	Features of the drug
Valsartan	Valz (Actavis Group hf.), Valsakor (KRKA), Valsartan-NW (North Star), Diovan (Novartis Pharma)	It is used in patients after an acute disturbance of coronary blood flow (myocardial infarction). It should be used carefully if it is necessary to drive vehicles, since it is possible to impair concentration of attention
Irbesartan	Aprovel (Sanofi Clear SS), Irsar (Kanonpharma production CJSC)	Not recommended for use in patients with primary hyperaldosteronism, in the case of high stages of chronic renal failure, in patients who have recently undergone a kidney transplant
Candesartan	Angiakand (Kanonfarma production CJSC), Ordiss (Teva), Xarten (VERTEX CJSC)	Dizziness and increased fatigue may occur during treatment. This should be taken into account before starting to work with machinery or driving.
Losartan	Lorista (Krka-Rus), Vazotenz (CNViTi PHARMA LIMITED), Lozap (Zentiva a.s)	Most often prescribed. It has an additional uricosuric effect. May be recommended in combination therapy for gout
Telmisartan	Telsartan (Dr. Reddy "s), Mikardis (Boehringer Ingelheim Pharma)	Reliably prevents the development of acute disorders of cerebral circulation and acute disorders of coronary blood flow (myocardial infarction), has a pronounced nephroprotective effect

Before starting the use of such medicines, it is imperative to consult a doctor.

Which is converted from its precursor serum globulin synthesized by the liver. Angiotensin is essential for the hormonal renin-angiotensin system, the system that controls blood volume and pressure in the human body.

The substance angiotensinogen belongs to the class of globulins, it consists of more than 400. Its production and release into the blood is constantly produced by the liver. The level of angiotensin can increase under the influence of angiotensin II, thyroid hormone, estrogen, plasma corticosteroids. When blood pressure drops, it acts as a stimulating factor for the production of renin, releasing it into the blood. This process triggers the synthesis of angiotensin.

Angiotensin I and angiotensin II

Under influence renin the following substance is formed from angiotensinogen - angiotensin I... This substance does not carry any biological activity, its main role is to be a precursor angiotensin II... The last hormone is already active: it ensures the synthesis of aldosterone, constricts blood vessels. This system is a target for drugs that lower, as well as for many inhibitory agents that reduce the concentration of angiotensin II.

The role of angiotensin in the body

This substance is strong vasoconstrictor ... This means that it also narrows the arteries, which in turn leads to an increase in blood pressure. This activity is due to the chemical bonds that are formed when the hormone interacts with a special receptor. Also among the functions related to the cardiovascular system, aggregation platelets, regulation of adhesion and prothrombotic effect. This hormone is responsible for those that arise in our body. It causes an increase in secretion in neurosecretory cells in such a part of the brain as hypothalamus, as well as the secretion of adrenocorticotropic hormone in pituitary gland... This results in a rapid release of norepinephrine. Hormone aldosterone , secreted by the adrenal glands, is released into the blood precisely due to angiotensin. Plays an important role in maintaining electrolyte and water balance, renal hemodynamics. The retention of sodium by this substance is due to its ability to act on the proximal tubules. In general, it is able to catalyze the glomerular filtration response by increasing renal pressure and constricting the renal efferent arterioles.

To determine the level of this hormone in the blood, a routine blood test is taken, like any other hormone. Its excess may indicate an increased concentration estrogen observed when using oral contraceptive pills and during, after binephrectomy, Itsenko-Cushing's disease may be a symptom of the disease. A decreased level of angiotensin is observed with glucocorticoid insufficiency, for example, with liver disease, Addison's disease.

Tangiotensin is a hormone produced by the kidneys that acts to constrict blood vessels. With increased concentration, blood pressure may rise. In this case, drugs that block the action of the hormone will be effective.

General information

Angiotensin receptor blockers (ARBs) are a new class of drugs that regulate and normalize blood pressure. They are not inferior in effectiveness to drugs with a similar spectrum of action, but unlike them, they have one indisputable plus - they practically have no side effects.

Among the positive properties of drugs, it can also be noted that they have a beneficial effect on the prognosis of a patient suffering from hypertension, are able to protect the brain, kidneys and heart from damage.

The most common groups of drugs are:

• sartans;
• angiotensin receptor antagonists;
• angiotensin receptor blockers.

Research on these drugs, at the moment, is still only in the initial stage and will continue for at least another 4 years. There are some contraindications to the use of angiotensin 2 receptor blockers.

The use of drugs is unacceptable during pregnancy and during lactation, with hyperkalemia, as well as in patients with severe renal failure and bilateral renal artery stenosis. Do not use these drugs for children.

Classification of drugs

According to their chemical constituents, angiotensin receptor blockers can be divided into 4 groups:

• Telmisartan. Non-biphenyl derivative of tetrazole.
• Eprosartan. Non-biphenyl nettetrazole.
• Valsartan. Non-cyclic compound.
• Losartan, Candesartan, Irbesartan. This group belongs to biphenyl tetrazole derivatives.

There are many trade names for sartans. Some of them are shown in the table:

How do blockers work?

During the time when blood pressure begins to decrease in the kidneys, renin is produced against the background of hypoxia (lack of oxygen). It affects the inactive angiotensinogen, which is transformed into angiotensin 1. It is acted upon by the angiotensin-converting enzyme, which is converted into angiotensin 2.

By binding to receptors, angiotensin 2 dramatically increases blood pressure. ARA act on these receptors, which is why the pressure decreases.

Angiotensin receptor blockers not only fight hypertension, but also have the following effect:

• reduction of left ventricular hypertrophy;
• reduction of ventricular arrhythmia;
• decrease in insulin resistance;
• improved diastolic function;
• decrease in microalbuminuria (excretion of protein in the urine);
• improving kidney function in patients with diabetic nephropathy;
• improved blood circulation (with chronic heart failure).

Sartans can be used to prevent structural changes in kidney and heart tissues, as well as atherosclerosis.

In addition, ARA may contain active metabolites. In some drugs, active metabolites last longer than the drugs themselves.

Indications for use

The use of angiotensin 2 receptor blockers is recommended for patients with the following pathologies:

• Arterial hypertension. Essential hypertension is the main indication for the use of sartans. Angiotensin receptor antagonists are well tolerated by patients and can be compared to placebo. Virtually do not cause uncontrolled hypotension. Also, these drugs, unlike beta-blockers, do not affect metabolic processes and sexual function, there is no arrhythmogenic effect. In comparison with angiotensin-converting enzyme inhibitors, ARBs practically do not cause cough and angioedema, do not increase the concentration of potassium in the blood. Angiotensin receptor blockers rarely induce drug tolerance in patients. The maximum and lasting effect of taking the drug is observed after two to four weeks.
• Kidney damage (nephropathy). This pathology is a complication of hypertension and / or diabetes mellitus. The improvement in prognosis is affected by a decrease in the excreted protein in the urine, which slows down the development of renal failure. Recent studies have shown that ARA reduces proteinuria (excretion of protein in the urine) by protecting the kidneys, but these results are not yet fully proven.
• Heart failure. The development of this pathology is due to activity. At the very beginning of the disease, it improves the activity of the heart, performing a compensatory function. During the development of the disease, myocardial remodeling occurs, which ultimately leads to its dysfunction. Treatment with angiotensin receptor blockers in heart failure is due to the fact that they are able to selectively suppress the activity of the renin-angiotensin-aldosterone system.

In addition, among the indications for the use of angiotensin receptor blockers are the following diseases:

• myocardial infarction;
• diabetic nephropathy;
• metabolic syndrome;
• atrial fibrillation;
• intolerance to ACE inhibitors.

Additional effects

Among the actions of angiotensin 2 receptor blockers, there is also a reduced level of low density lipoprotein cholesterol and total cholesterol, improving lipid metabolism. Also, these drugs reduce the levels of uric acid in the blood.

Sartans have the following additional clinical effects:

• arrhythmic effect;
• protection of cells of the nervous system;
• metabolic effects.

Side effects of taking blockers

Angiotensin 2 receptor blockers are well tolerated by the patient's body. In principle, these drugs do not have specific side effects, unlike other groups of drugs of similar action, but they can cause allergic reactions, like any other drug.

Among the few side effects, the following can be noted:

• dizziness;
• headache;
• insomnia;
• abdominal pain;
• nausea;
• vomiting;
• constipation.

In rare cases, the patient may observe such disorders:

• soreness in the muscles;
• joint pain;
• increased body temperature;
• manifestation of ARVI symptoms (runny nose, cough, sore throat).

Sometimes there are side effects from the genitourinary and cardiovascular systems.

Application features

As a rule, drugs that block angiotensin receptors are produced in the form of tablets, which can be drunk regardless of food intake. The maximum stable concentration of the drug is achieved after two weeks of regular administration. The period of elimination from the body is at least 9 hours.

Angiotensin 2 blockers may differ in their spectrum of action.

Features of taking Losartan

The course of treatment for hypertension is 3 weeks or more, depending on individual characteristics.

In addition, this drug lowers the concentration of uric acid in the blood and removes sodium water from the body. The dosage is adjusted by the attending physician based on the following indicators:

• Combined treatment involving the use of this drug with diuretics involves the use of no more than 25 mg. per day.
• If side effects occur, such as headache, dizziness, lowering blood pressure, the dosage of the drug should be reduced.
• In patients with hepatic and renal insufficiency, the drug is prescribed with caution and in small doses.

Contraindications to taking Valsartan

The drug acts only on AT-1 receptors, blocking them. The effect of a single dose is achieved after 2 hours. It is prescribed only by the attending physician, since there is a risk that the drug can harm.

Caution should be exercised when using the drug in patients who have the following pathologies:

• Bile duct obstruction. The drug is excreted from the body with bile, therefore, the use of valsartan is not recommended for patients who have disturbances in the work of this organ.
• Renovascular hypertension. In patients with this diagnosis, monitoring of serum urea levels, as well as creatinine, is necessary.
• Imbalance of water-salt metabolism. In this case, correction of this violation is mandatory.

Important! When using Valsartan, the patient may experience symptoms such as cough, swelling, diarrhea, insomnia, decreased sexual function. While taking the drug, there is a risk of developing various viral infections.

The drug should be taken with caution during work that requires maximum concentration of attention.

Prescribing Ibersartan

The action of the drug is aimed at:

• reducing the load on the heart;
• elimination of the vasoconstrictor effect of angiotensin 2;
• decline.

The effect of taking this drug is achieved after 3 hours. After completing the course of taking Ibersartan, blood pressure systematically returns to its original value.

Ibersartan does not prevent the development of atherosclerosis, unlike most angiotensin receptor antagonists, since it does not affect lipid metabolism.

Important! The drug assumes daily intake at the same time. If you miss an appointment, doubling the dose is strongly discouraged.

Adverse reactions when taking Ibersartan:

• headache;
• nausea;
• dizziness;
• weakness.

The effectiveness of Eprosartan

In the treatment of hypertension, it has a mild and persistent effect throughout the day. When you stop taking, no sudden pressure surges are observed. Eprosartan is prescribed even for diabetes mellitus, as it does not affect blood sugar levels. The drug can also be taken by patients with renal impairment.

Eprosartan has the following side effects:

• cough;
• runny nose;
• dizziness;
• headache;
• diarrhea;
• chest pain;
• dyspnea.

Adverse reactions are usually short-term and do not require dose adjustment or complete discontinuation of the drug.

Features of taking Telmisartan

The most powerful drug among the sartans. Displaces angiotensin 2 from the connection with AT-1 receptors. It can be prescribed to patients with impaired renal function, while the dosage does not change. However, in some cases, it can cause hypotension even in small doses.

Telmisartan is contraindicated in patients with the following disorders:

• primary aldosteronism;
• severe violations of liver and kidney function.

Do not prescribe the drug during pregnancy and lactation, as well as children and adolescents.

Among the side effects of Telmisartan use are:

• dyspepsia;
• diarrhea;
• angioneurotic edema;
• back pain;
• muscle pain;
• the development of infectious diseases.

Telmisartan belongs to a group of drugs that act by accumulation. The maximum effect of the application can be achieved after a month of regular intake of the drug. Therefore, it is important not to adjust the dosage yourself in the first weeks of admission.

Despite the fact that drugs blocking angiotensin receptors have a minimum of contraindications and side effects, they should be taken with caution due to the fact that these drugs are still under study. The correct dose for the treatment of high blood pressure in a patient can be prescribed exclusively by the attending physician, since self-medication can lead to undesirable consequences.

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Angiotensin II synthesis inhibitors

This is a new group of drugs that are involved in the metabolism of the aldosterone-angiotensin-renin system.
Captopril (kapoten) inhibits an enzyme that converts inactive angiotensin I to active pressor angiotensin II and destroys the vasodepressor bradykinin (Scheme 11). Captopril lowers blood pressure at any initial level of renin, but to a greater extent at an elevated one, which makes it possible to use the drug for renovascular hypertension. Captopril increases cardiac output, decreases left ventricular end-diastolic pressure, and decreases vascular resistance. The antihypertensive effect is potentiated by the administration of diuretics.

Scheme 11

Captopril is rapidly absorbed from the gastrointestinal tract. Food intake reduces its bioavailability by 35-40%. Only 25-30% of the drug binds to plasma proteins. Its maximum concentration in the blood is achieved within 1 hour. The half-life of captopril is 4 hours, 50% of the drug dose is excreted by the kidneys unchanged. Captopril does not accumulate in the body.
The drug is administered orally starting at a dose of 25 mg 2 times a day. If necessary, the dose is increased to 50 mg 2-4 times a day. The maximum daily dose of captopril is 450 mg / day, and in severe hypertension - 300-600 mg / day.
The most common side effects are skin rashes and impaired taste. After stopping treatment, these symptoms disappear.
Enalaprilmaleate also reduces the activity of the angiotensin-converting enzyme, the level of renin and angiotensin II in the blood plasma.
Enalaprilmaleate, when taken orally, is hydrolyzed and converted into enalaprilat. Its bioavailability is about 40%. After oral administration in healthy and patients with arterial hypertension, the drug is detected in the blood after 1 hour and the concentration reaches a maximum after 3-4 hours.In the blood enalaprilmaleate binds to proteins by 50%, is excreted in the urine, its renal clearance is 150 ± 44 ml / min ... The elimination of enalapril from the body slows down with a decrease in glomerular filtration.
The drug is prescribed for arterial hypertension, mainly of renovascular origin, and heart failure at a dose of 1-2 mg 3-4 times a day. Side effects are very rare.

Other antihypertensive drugs

Ganglion blocking drugs

These funds block both sympathetic and parasympathetic nodes at the same time. In connection with the blockade of parasympathetic nodes, paralytic ileus, paresis of the gallbladder, disturbances in the accommodation of the eyes, and impotence may occur. Therefore, these drugs are almost never used for a long time, but only parenterally in acute situations - hypertensive crises. They are contraindicated in acute myocardial infarction, cerebral artery thrombosis, pheochromocytoma.
Ganglion blocking drugs include pentamine, arfonade, and benzohexonium.
Benzohexonium (hexonium) - H-anticholinergic blocker of sympathetic and parasympathetic ganglia. The hypotensive effect of benzohexonium is explained by the suppression of the sympathetic ganglia, which entails the expansion of arterial and venous vessels. The blockade of the parasympathetic ganglia causes inhibition of the motility of the digestive tract, inhibition of the secretion of the gastric and salivary glands, which determines the main undesirable effects of the drug.
Benzohexonium reduces the tone of arterioles and reduces the total peripheral resistance. The venous tone and venous pressure drop significantly, as well as the pressure in the pulmonary artery and right ventricle. As a result of the deposition of blood in the dilated veins of the abdominal cavity and extremities, the mass of circulating blood rapidly decreases, therefore, orthostatic hypotension is observed in the first 2 hours after drug administration. A decrease in venous return of blood leads to unloading of the heart, an improvement in myocardial contractile function, which is accompanied by an increase in cardiac output. Benzohexonium has a sedative effect on the central nervous system, inhibits the functional state of the sympathetic-adrenal system, inhibits the function of the thyroid gland and increases insulin sensitivity in patients with diabetes mellitus.

Benzohexonium is injected intramuscularly or subcutaneously in 0.5-1 ml of a 2.5% solution (12.5-25 mg). A single dose should not exceed 100 mg, and a daily dose should not exceed 400 mg. Addiction develops to the drug.
The drug is indicated for hypertensive crises, accompanied by left ventricular failure, retinopathy, encephalopathy or cerebral hemorrhage.
Pentamine is a ganglion blocking drug, the mechanism of action and pharmacodynamics of which are the same as benzohexonium.
Pentamin is prescribed for intravenous slow administration at a dose of 0.2-0.5-0.75 ml of a 5% solution diluted in 20 ml of isotonic sodium chloride solution or 5% glucose solution. 0.3-0.5-1 ml of 5% pentamine solution is injected intramuscularly. Blood pressure decreases within 5-15 minutes with a maximum effect after 30 minutes, the effect lasts 4 hours, sometimes up to 12 hours.

Arfonad (trimetaphan camphorsulfonate) is a fast-acting ganglion blocker.
Arfonad is used in the form of a 0.1% solution for intravenous drip infusion (500 mg of arfonade per 500 ml of 5% glucose solution). The rate of administration of the drug is regulated by the level of blood pressure. Its action begins in 1 - 2 minutes, reaches a maximum in 5 minutes and ends 10 minutes after the termination of the administration.
The drug is indicated for an urgent decrease in blood pressure in acute hypertensive encephalopathy, cerebral edema, dissecting aortic aneurysm.
Aminazine (chlorpromazine) is a phenothiazide derivative that belongs to the group of neuroleptics (large tranquilizers).
The antihypertensive effect of the drug is due to the a-adrenergic blocking action. In the mechanism of hypotension, other effects of chlorpromazine are also important: inhibition of the centers of the hypothalamus and antispasmodic properties. Aminazine is a strong sedative, reduces psychomotor agitation, has an antiemetic effect, potentiates the effect of hypnotics, drugs, analgesics and local anesthetics, and also reduces capillary permeability, has a weak antihistamine effect.
The hypotensive effect of chlorpromazine is often accompanied by reflex tachycardia. With prolonged use, addiction develops to it. This applies to sedative, hypotensive and some other effects, but not antipsychotic action.
Aminazine is poorly absorbed from the gastrointestinal tract. The duration of action after a single injection is about 6 hours. In the body, a significant part of chlorpromazine undergoes biotransformation. The drug itself and various products of its transformation are excreted by the kidneys and intestines. Their excretion is slow, over many days.
For the treatment of hypertensive crisis, 1 ml of 2.5% chlorpromazine solution in 20 ml of 5% glucose solution is injected intravenously or in a stream. When the drug is injected, the irritating properties of] aminazine should be taken into account: with intravenous administration, damage to the endothelium is possible, with intramuscular administration, the occurrence of painful infiltrates. To avoid these phenomena, chlorpromazine solutions are diluted with solutions of novocaine, glucose, isotonic sodium chloride solution.
Side effects during treatment with chlorpromazine include hypotension, allergic reactions of the skin and mucous membranes, swelling of the face and extremities. There are known cases of jaundice, agranulocytosis, skin pigmentation, parkinsonism.
The drug is indicated in hypertensive crisis to relieve agitation and gag reflexes.
Aminazine is contraindicated in liver cirrhosis, hepatitis, hemolytic jaundice, nephritis, dysfunction of hematopoietic organs, progressive systemic diseases of the brain and spinal cord, decompensated heart disease, thromboembolic disease. It is impossible to prescribe chlorpromazine to persons who are in a coma, including in cases associated with the use of barbiturates, alcohol, drugs, as well as for the purpose of arresting excitation in acute brain injuries.
Magnesium sulfate is a myotropic antispasmodic. The hypotensive effect of the drug is associated with a direct expansion of the smooth muscles of the blood vessels. In addition, when administered parenterally, it has a calming effect on the central nervous system. Depending on the dose of magnesium sulfate, sedative, anticonvulsant, hypnotic, or narcotic effects can be observed. In large doses, the drug reduces the excitability of the respiratory center and can cause respiratory paralysis. The drug is poorly absorbed from the gastrointestinal tract, therefore, when administered orally, the hypotensive effect is not manifested. Magnesium sulfate is excreted by the kidneys; in the process of its excretion, an increase in diuresis is noted.
In hypertensive crises, 10-20 ml of 20-25% magnesium sulfate solution is slowly injected intramuscularly or intravenously. Given the hypotensive and anticonvulsant effect of the drug, it is prescribed for eclampsia and encephalopathy.
In case of an overdose of magnesium sulfate, respiratory paralysis is possible (calcium salts are used as an antidote, for example, 5-10 ml of a 10% solution of calcium chloride). In large doses, the drug can have a curariform effect (suppression of neuromuscular transmission of excitation).
Dibazol is a myotropic antispasmodic. It has an antispasmodic effect on smooth muscle organs. Gives a hypotensive effect by expanding peripheral vessels and reducing cardiac output. The hypotensive activity of dibazol is very moderate, and its effect is short-lived.
In hypertensive crises (mainly with a hypo- or eukinetic type of blood circulation), dibazol is prescribed intravenously, 6 ml of a 1% solution or 6-12 ml of a 0.5% solution. The drug is well tolerated by patients.

Calcium antagonists

In recent years, attention has been paid to the ability of nifedipine, verapamil and diltiazem to reduce peripheral resistance, which is associated with a decrease in Ca ++ entry into vascular smooth muscle cells. Therefore, Ca ++ antagonists have found application in the treatment of severe hypertension in individuals with low blood renin activity and in old age (due to the cardioprotective effect). For treatment, nifedipine is used at a dose of 20-60 mg / day, often in combination with dopegit or B-blockers or verapamil at a dose of 320 mg / day. Diltiazem is prescribed at 90-180 mg / day.

Pioneering studies by Page, Helmer and Braun-Menendez in the 1930s showed that renin is an enzyme that breaks down α 2 -globulin (angiotensinogen) to form a decapeptide (angiotensin I). The latter is then cleaved by an angiotensin-converting enzyme (ACE) to form an octapeptide (angiotensin II), which has potent vasoconstrictor activity. In those same years, Goldblatt found that a decrease in blood flow in the kidneys of experimental animals leads to an increase in blood pressure. In the future, these two facts were connected with each other: a decrease in blood flow in the kidneys stimulates the renin-angiotensin system, which leads to an increase in blood pressure. This scheme forms the foundation of modern concepts of blood pressure regulation.

Renin

Smooth muscle cells at the entry point of the bringing arteriole into the renal glomerulus ("juxtaglomerular") have a secretory function; they produce and secrete renin, a proteolytic enzyme with a molecular weight of about 40,000. The juxtaglomerular cells are adjoined by specialized cells of the thick ascending knee of Henle's loop, located in the cortex of the kidneys. This area of \u200b\u200bthe nephron is called a dense spot. Juxtaglomerular cells and a dense spot together form the juxtaglomerular apparatus, and their interaction plays a critical role in the regulation of renin secretion.
Renin synthesis involves a number of steps starting with the translation of renin mRNA into preprorenin. The N-terminal sequence of preprorenin (of 23 amino acid residues) directs the protein to the endoplasmic reticulum, where it is cleaved to form prorenin. Prorenin is glycosylated in the Golgi apparatus and is either directly secreted into the blood in an unregulated manner, or is packaged into secretory granules where it is converted into active renin. Although prorenin accounts for as much as 50-90% of total blood renin, its physiological role remains unclear. Outside of the kidneys, it practically does not turn into renin. With microangiopathic complications of type 1 diabetes mellitus, the level of prorenin in plasma increases slightly.

The release of renin from secretory granules into the blood is controlled by three main mechanisms:

1. baroreceptors of the walls of the bearing arterioles, which are stimulated with a decrease in perfusion pressure; this effect is probably mediated by local production of prostaglandins;
2. receptors of the heart and large arteries, which activate the sympathetic nervous system, leading to an increase in the level of catecholamines in the blood and direct nervous stimulation of juxtaglomerular cells (through β 1 -adrenergic receptors);
3. cells of the dense spot, which are stimulated with a decrease in the concentration of Na + and CG ions in the tubular fluid entering this segment of the nephron. The main mediator of this effect is apparently the SG ions.

Once in the blood, renin cleaves the decapeptide angiotensin I from the N-terminal sequence of angiotensinogen. Then angiotensin I under the action of ACE is converted into the octapeptide angiotensin II. The concentration of ACE is highest in the lungs. It is also present on the luminal membrane of vascular endothelial cells, in the renal glomeruli, brain and other organs. Various angiotensinases, localized in most tissues, rapidly degrade angiotensin II, and its plasma half-life is less than 1 minute.

Angiotensinogen

Angiotensinogen (renin substrate) is a 2 -globulin secreted by the liver. The concentration of this protein (molecular weight about 60,000) in human plasma is 1 mmol / L. Normally, the concentration of angiotensinogen is below the Vmax of the reaction catalyzed by renin. Therefore, with an increase in the concentration of angiotensinogen, the amount of angiotensin formed at the same level of renin in the plasma should increase. In hypertension, the plasma angiotensinogen content is increased, and this disease is apparently linked to a variant of the angiotensinogen gene allele. Glucocorticoids and estrogens stimulate hepatic production of angiotensinogen, which leads to an increase in blood pressure when taking oral contraceptives containing estrogens.
With a decrease in the content of Na + in the body, accompanied by an increase in the level of renin in the plasma, the metabolic rate of angiotensinogen increases sharply. Since the concentration of its degradation products does not change under such conditions, this increase is apparently compensated for by increased hepatic production of angiotensinogen. The mechanism of this increase remains unclear, although it is known that angiotensin II stimulates the production of angiotensinogen.

Angiotensin converting enzyme

ACE (dipeptidyl carboxypeptidase) is a glycoprotein with a molecular weight of 130,000-160000 that cleaves dipeptides from many substrates. In addition to angiotensin I, these substrates include bradykinin, enkephalins, and substance P. ACE inhibitors are widely used to prevent the formation of angiotensin II in the blood and thereby block its effects. Since ACE acts on a variety of substrates, the results of inhibition of this enzyme are not always limited to changes in the activity of the renin-angiotensin system. Indeed, in the hypotensive effect of ACE inhibitors, an increase in the level of kinins, which promote the release of nitric oxide from the vascular endothelium, may play a role. Bradykinin antagonists weaken the hypotensive effect of ACE inhibitors. An increase in the level of kinins can also mediate another effect of ACE inhibitors, namely, an increase in tissue sensitivity to insulin and a decrease in blood glucose levels in patients with type 2 diabetes mellitus. In addition, kinin accumulation may underlie two of the most important side effects of ACE inhibitors: cough, Quincke's edema, and anaphylaxis.
In addition to ACE, serine proteases, called chymases, can convert angiotensin I to angiotensin II. These enzymes are found in various tissues; their activity is especially high in the ventricles of the heart. Thus, there is also an ACE-independent mechanism for the formation of angiotensin II.

Angiotensin II

Like other peptide hormones, angiotensin II binds to receptors localized on the plasma membrane of target cells. Two classes of angiotensin II receptors are described - AT1 and AT2; their mRNAs are isolated and cloned. Almost all known cardiovascular, renal, and adrenal effects of angiotensin II are realized through AT1 receptors, while AT2 receptors can mediate the effect of this peptide on cell differentiation and growth. Receptors of both classes contain seven transmembrane domains. AT1 are conjugated with a G-protein, which activates phospholipase C, thereby enhancing the hydrolysis of phosphoinositide to form inositol triphosphate and diacylglycerol. These "second messengers" trigger a cascade of intracellular reactions, including an increase in the concentration of calcium in cells, activation of protein kinases, and, probably, a decrease in the intracellular concentration of cAMP. The mechanism of signal transmission from AT2 receptors remains unknown.
Angiotensin II is a potent pressor factor; by narrowing the arterioles, it increases the total peripheral resistance. Vasoconstriction occurs in all tissues, including the kidney, and plays a role in the mechanism of autoregulation of renal blood flow. In addition, angiotensin II increases the heart rate and strength of the heart.
Acting directly on the adrenal cortex, angiotensin II stimulates the secretion of aldosterone, and is the most important regulator of the secretion of this hormone. It plays a key role in the regulation of Na + balance. For example, a decrease in the volume of extracellular fluid with insufficient intake of Na + stimulates the renin-angiotensin system. On the one hand, the vasoconstrictive effect of angiotensin II helps maintain blood pressure in conditions of a reduced extracellular fluid volume, and on the other hand, angiotensin II stimulates the secretion of aldosterone, causing sodium retention, which contributes to the preservation of plasma volume.
With a chronic decrease in intravascular volume, characteristic of low Na + consumption, a constantly increased level of angiotensin II leads to a decrease in the number of AT1 receptors in the vessels, and the degree of vasoconstriction is less than expected. In contrast, the number of AT1 receptors in the glomerular zone of the adrenal cortex increases with a decrease in intravascular volume, and the secretion of aldosterone under the action of angiotensin II increases to a greater extent. It is assumed that the opposite effects of a chronic decrease in intravascular volume on the sensitivity of vessels and adrenal glands to angiotensin II are physiologically justified: under conditions of low Na + consumption, a sharp increase in aldosterone secretion increases the reabsorption of this ion in the kidneys without a significant increase in blood pressure. In some cases of hypertension, this "sodium modulation" of the sensitivity of the adrenal glands and blood vessels to angiotensin II is disturbed.
Angiotensin II enhances the response of peripheral vessels and the heart to sympathetic influences (by facilitating the secretion of norepinephrine by nerve endings and increasing the sensitivity of the vascular smooth muscle membrane to this transmitter). In addition, under the influence of angiotensin II, the secretion of adrenaline by the adrenal medulla increases.
The clinic uses a number of angiotensin II antagonists, which act only on AT1 receptors, without affecting the effects mediated by AT2 receptors. On the other hand, ACE inhibitors reduce the activity of both classes of receptors. Angiotensin receptor blockers do not affect bradykinin levels. Since ACE inhibitors lower blood pressure in part by increasing bradykinin levels, and angiotensin II is produced even with ACE blockade, the combination of ACE inhibitors with ATl blockers can lower blood pressure to a greater extent than either of these drugs alone.
The blockade of the formation and peripheral effects of angiotensin II is used therapeutically. For example, an increase in angiotensin II levels in congestive heart failure with low cardiac output promotes salt and water retention and, by inducing vasoconstriction, increases peripheral vascular resistance, and thereby post-cardiac stress. ACE inhibitors or angiotensin receptor blockers dilate peripheral vessels, improve tissue perfusion and myocardial performance, and promote the excretion of salt and water through the kidneys.

The effect of angiotensin II on the brain

Angiotensin II is a polar peptide that does not cross the blood-brain barrier. However, it can affect the brain by acting through structures adjacent to the cerebral ventricles and lying outside the blood-brain barrier. Of particular importance in the action of angiotensin II are the subforinal organ, the vascular organ of the terminal plate and the caudal part of the bottom of the IV ventricle.
Angiotensin II produces intense thirst. The receptors mediating this effect are located mainly in the subforonic organ. Under the influence of angiotensin II, the secretion of vasopressin also increases (mainly due to an increase in plasma osmolality). Thus, the renin-angiotensin system can play an important role in the regulation of water balance, especially in hypovolemic conditions.
A number of models of the pathogenesis of arterial hypertension suggest the formation of angiotensin II directly in the brain. However, the degree of increase in blood pressure due to the cerebral effects of angiotensin II is much less than that associated with the direct effect of this peptide on the vessels. In most animals, receptors mediating the cerebral hypertensive effects of angiotensin II are located in the area postrema. Other central effects of angiotensin II include stimulation of ACTH secretion, decreased ARP, and increased salt cravings, especially in association with increased mineralocorticoid levels. The significance of all these (and other) central effects of angiotensin remains to be seen.

Local renin-angiotension systems

All components of the renin-angiotensin system are present not only in the general bloodstream, but also in various tissues, and therefore angiotensin II can be formed locally. These tissues include the kidneys, brain, heart, ovaries, adrenal glands, testes, and peripheral vessels. In the kidney, angiotensin II directly stimulates Na + reabsorption in the upper segments of the proximal tubules (in part due to activation of Na + / H + countertransport on the luminal membrane). Angiotensin II of local or systemic origin also plays a key role in maintaining GFR during hypovolemia and decreased arterial blood flow. Under the influence of angiotensin II, the outflowing arterioles are narrowed to a greater extent than the inflowing arterioles, which leads to an increase in the hydraulic pressure in the capillaries of the renal glomeruli and prevents a decrease in GFR with a decrease in renal perfusion.

Renin-angiotensin system and arterial hypertension

Hypertonic disease

(module direct4)

Blood pressure depends both on the minute volume of the heart and on the peripheral vascular resistance. Essential hypertension is caused by an increase in peripheral vascular resistance, which, in turn, is determined by the complex interaction of many systemically and locally produced hormones and growth factors, as well as neurogenic influences. However, the specific factor (or factors) underlying the pathogenesis of hypertension has not yet been established. The known data on an increase in blood pressure with impaired renal perfusion and an increase in renin secretion allow us to perceive the role of the renin-angiotensin system in the etiology of hypertension.
Back in the early 1970s, Laragh et al. proposed to evaluate the relative role of vasoconstriction and an increase in intravascular volume in the pathogenesis of hypertension according to ARP. With increased ARP, vasoconstriction was considered the leading mechanism for the development of this disease, and with low ARP, an increase in intravascular volume. While this view is theoretically justified, it is not always supported by hemodynamic studies. In addition, agents affecting the renin-angiotensin system (ACE inhibitors, angiotensin receptor blockers) help even with hypertension with low ARP.
As noted above, a diet low in Na + increases the adrenal response to angiotensin II, while simultaneously decreasing vascular sensitivity to this peptide. Na + loading has the opposite effect. In a healthy person consuming a large amount of Na +, changes in the reactivity of the adrenal glands and blood vessels contribute to an increase in renal blood flow and a decrease in Na + reabsorption in the kidneys. Both facilitate the elimination of excess Na + from the body. In almost 50% of cases of hypertension with normal or increased ARP, a violation of the ability to remove sodium load is found. It is assumed that the main defect is associated either with the local production of angiotensin II, or with a violation of its receptors, as a result of which fluctuations in Na + consumption do not change the reactivity of the target tissues. ACE inhibitors, reducing the level of angiotensin I, restore the reactivity of the adrenal glands and blood vessels in such cases.
In about 25% of patients, ARP is reduced. Arterial hypertension with low ARP is more often found in representatives of the black race and the elderly. It is assumed that in these cases, blood pressure is especially sensitive to salt, and its reduction is most easily achieved with the help of diuretics and calcium antagonists. Although it was previously believed that ACE inhibitors are ineffective in hypertension with low ARP, recent studies show that ARP value cannot be a predictor of the effectiveness of drugs in this class. It is possible that the effectiveness of ACE inhibitors in such cases is associated with an increase in the level of bradykinin or with inhibition of local production of angiotensin II in the kidneys, brain and blood vessels. This is supported by recent studies on transgenic rats (carriers of the murine renin gene). In such rats, a severe and often lethal form of arterial hypertension was observed, which could be weakened by ACE inhibitors or angiotensin receptor blockers. Although ARP, as well as the levels of angiotensin II in plasma and renin in the blood of the renal vein in these animals were reduced, the content of renin in the adrenal glands and the level of prorenin in plasma were increased, and adrenalectomy led to a decrease in blood pressure. Thus, ARP in systemic blood does not reflect the state of the local renin-angiotensin system and its role in the pathogenesis of arterial hypertension.
Recent molecular studies also confirm the involvement of the renin-angiotensin system in the pathogenesis of hypertension. In siblings, a linkage was found between the allele of the angiotensinogen gene and hypertension. A correlation was found between the plasma angiotensinogen level and blood pressure; in hypertension, the concentration of angiotensinogen is increased. Moreover, if parents suffer from hypertension, then the level of angiotensinogen is increased in their children with normal blood pressure.

Renovascular hypertension

Renovascular hypertension is the most common cause of renin-dependent high blood pressure. According to various sources, it is found in 1-4% of patients with arterial hypertension and is the most curable form of this disease. Renal artery disease and renovascular hypertension are less common among African Americans than among Caucasians. Atherosclerosis or fibromuscular hyperplasia of the walls of the renal arteries leads to a decrease in renal perfusion and increased production of renin and angiotensin II. Blood pressure rises, but high angiotensin II levels suppress renin secretion by the contralateral kidney. Therefore, the total ARP may remain normal or increase only slightly. An increase in blood pressure can be associated with other anatomical reasons: kidney infarction, cysts, hydronephrosis, etc.
Given the relatively low frequency of such cases, screening of all patients with high blood pressure for renovascular hypertension is inappropriate. First, you should make sure of the "non-idiopathic" nature of arterial hypertension in this patient.

Renovascular hypertension should be suspected in the following cases:

1. with severe hypertension (diastolic blood pressure\u003e 120 mm Hg) with progressive renal failure or refractoriness to aggressive drug therapy;
2. with a rapid increase in blood pressure or malignant hypertension with stage III or IV retinopathy;
3. with moderate or severe hypertension in patients with diffuse atherosclerosis or accidentally identified asymmetry in the size of the kidneys;
4. with an acute increase in plasma creatinine (due to unknown reasons or during treatment with ACE inhibitors);
5. with an acute increase in previously stable blood pressure;
6. when listening to a systolic-diastolic murmur above the abdominal aorta;
7. with the development of hypertension in people younger than 20 years old or older than 50 years;
8. with moderate or severe hypertension in people with repeated episodes of pulmonary edema;
9. with hypokalemia against a background of normal or increased ARP in the absence of diuretic therapy;
10. in the absence of arterial hypertension in the family history.

Acute deterioration of renal function during treatment with ACE inhibitors or angiotensin receptor blockers indicates bilateral renal artery stenosis. In this situation, the pressure in the glomeruli of both kidneys is maintained by angiotensin II, which constricts the efferent arterioles, and elimination of this effect leads to a decrease in intraglomerular pressure and GFR.
The standard method for diagnosing renal vascular disease is renal angiography. However, this study carries the risk of acute tubular necrosis, and therefore non-invasive renal vascular imaging and pharmacological tests are used. Modern methods of diagnostics of renovascular pathology include: 1) stimulation test with captopril and determination of ARP; 2) renography with captopril; 3) Doppler study; 4) magnetic resonance angiography (MRA); 5) spiral CT.
By itself, an increase in the basal level of renin in plasma does not prove the presence of renovascular hypertension, since it is increased only in 50-80% of such patients. Normally, the ACE inhibitor captopril, by blocking the action of angiotensin II through a negative feedback mechanism, causes reactive hyperreninemia. In patients with renal artery stenosis, this reaction is enhanced, and the level of renin, determined 1 hour after taking captopril, is much higher than in hypertensive disease. The sensitivity and specificity of this test are 93-100% and 80-95%, respectively. It is less sensitive in people of the black race, in young patients, in patients with renal insufficiency or receiving antihypertensive therapy.
Renal artery stenosis stimulates the renin-angiotensin system of the ipsilateral kidney, and angiotensin II, by narrowing the efferent arterioles, contributes to the maintenance of intraglomerular pressure and GFR. ACE inhibitors (for example, captopril) decrease the production of angiotensin II and thereby lower glomerular pressure and GFR. Isotope scanning of the kidneys before and after taking captopril can detect unilateral renal ischemia. If the maximum accumulation of the isotope in one kidney is reduced or slowed down in comparison with the other, then this indicates a lesion of the renal vessels. The sensitivity of this test in patients at high risk for renal artery stenosis reaches 90%.
Recently, a combination of duplex ultrasound of the kidneys with measurement of renal arterial blood flow (Doppler) has been used to diagnose renal artery stenosis. The specificity of such a complex method exceeds 90%, but depends on the experience of the researcher. Gas accumulation in the intestines, obesity, recent surgery, or the presence of an accessory renal artery make it difficult to visualize stenosis. Doppler blood flow data can be used to calculate renal artery resistance and to decide which patient can benefit from revascularization.
In contrast to the old observations, in which the sensitivity of MRA was estimated at 92-97%, modern studies indicate only 62% of the sensitivity and 84% of the specificity of this method. MRA sensitivity is particularly low in renal artery stenosis associated with fibromuscular dysplasia. The most sensitive method for detecting renal artery stenosis is probably spiral CT; the sensitivity and specificity of this method in some studies reached 98% and 94%, respectively.
Due to the lack of sufficiently sensitive non-invasive methods that would completely eliminate renal artery stenosis, clinicians often have to decide when and how to examine the state of renal blood flow in patients with arterial hypertension. Mann and Pickering, based on the clinical suspicion index, proposed a practical patient selection algorithm for the diagnosis of renovascular hypertension and renal angiography. In patients of the moderate risk group, it is advisable to start with a Doppler study with the calculation of renal vascular resistance.
Patients with renovascular hypertension are shown anatomical correction of the renal vessels. If arteriography reveals narrowing of one or both renal arteries by more than 75%, this indicates the possibility of renal origin of arterial hypertension. The hemodynamic significance of stenosis can be judged by determining the level of renin in the blood of the renal vein on the side of the stenosis and comparing it with the level of renin in the blood flowing from the contralateral kidney. The ratio of these levels is usually considered significant more than 1.5, although a lower ratio does not exclude the diagnosis. Taking an ACE inhibitor prior to renal venous catheterization may increase the sensitivity of this test. Surgical treatment normalizes blood pressure in more than 90% of patients with renal artery stenosis and unilateral increase in renin secretion. However, angioplasty or surgery is effective in many patients with a renin ratio in both renal veins of less than 1.5. Therefore, it is no longer considered necessary to determine this ratio in case of significant renal artery stenosis. This indicator can be useful in bilateral stenosis or stenosis of segmental renal arteries, as it allows you to establish which kidney or its segment is the source of increased renin production.
The calculation of the renal artery resistance index [(1 - blood flow velocity at the end of diastole) / (maximum blood flow velocity in systole) x 100] according to the duplex Doppler study helps to predict the effectiveness of renal revascularization. With a resistance index of more than 80, surgery, as a rule, was unsuccessful. In about 80% of patients, kidney function continued to deteriorate, and a significant decrease in blood pressure was observed in only one patient. On the contrary, with a resistance index of less than 80, renal revascularization led to a decrease in blood pressure in more than 90% of patients. A high resistance index probably indicates damage to intrarenal vessels and glomerulosclerosis. Therefore, restoration of the patency of the main renal arteries in such cases does not reduce blood pressure and does not improve renal function. Recent studies have confirmed the absence of a decrease in blood pressure after revascularization in patients with severe renal artery stenosis (\u003e 70%) and reduced renal function (GFR< 50 мл/мин). Однако СКФ после реваскуляризации несколько увеличивалась.
Anatomical correction of the renal arteries is performed either by percutaneous angioplasty (with or without stenting), or by direct surgery. The question of the optimal treatment method remains open, as there have been no randomized trials comparing the results of angioplasty (with or without stenting), surgery, and drug therapy. In case of fibromuscular dysplasia, the method of choice is still angioplasty, which, according to various sources, cures 50-85% of patients. In 30-35% of cases, angioplasty improves the condition of patients, and only in less than 15% of cases it turns out to be ineffective. With atherosclerotic stenosis of the renal arteries, the choice of treatment is much more difficult. The success of the intervention depends on the location of the narrowing of the arteries. In general, if the main renal arteries are damaged, angioplasty gives the best results, and stenting is required if their orifices are narrowed. Angioplasty alone in atherosclerosis of the renal arteries eliminates arterial hypertension in 8-20% of patients, leads to a decrease in pressure in 50-60% of cases and is ineffective in 20-30% of cases. In addition, within 2 years after such a procedure, renal artery restenosis is observed in 8-30% of patients. Angioplasty is even less successful for bilateral renal artery disease or chronic arterial hypertension. To increase the efficiency of angioplasty, stents are used. According to a number of uncontrolled studies, a decrease in blood pressure in such cases is observed in 65-88% of patients, and restenosis develops only in 11-14% of them. When performing renal revascularization, it is necessary to take into account the risks of atheroembolism (associated with angiography), deterioration of renal function and nephrotoxicity (due to the use of iodinated X-ray contrast agents).
Another important issue is the assessment of the possibility of improving renal function after intervention, especially in bilateral renal artery stenosis with decreased renal blood flow and GFR, but a discussion of this issue is beyond the scope of this chapter. Treatment of patients with atherosclerotic stenosis of the renal artery requires the adoption of general measures to combat atherosclerosis - smoking cessation, achieving target blood pressure values \u200b\u200band eliminating lipid metabolism disorders. Recently it was shown that statins not only slow down, but also contribute to the regression of atherosclerotic lesions.
Surgical correction of renal artery stenosis is usually done by endarterectomy or bypass surgery. These methods, as a rule, are more effective than angioplasty, but the operation can be accompanied by higher mortality, especially in elderly patients with concomitant cardiovascular diseases. In most medical centers, renal revascularization is preferred by the method of percutaneous angioplasty with the installation of stents, especially for stenosis of the orifices of the renal arteries. Surgical revascularization is performed only if angioplasty is ineffective or, if necessary, simultaneous surgery on the aorta.
In cases of general poor condition of the patient or doubts about the diagnosis, drug treatment is used. Recent randomized controlled trials have shown that renal revascularization in patients with suspected renovascular hypertension receiving conservative drug treatment does not always give the desired results. ACE inhibitors and selective AT1 receptor antagonists are especially effective, although, as already mentioned, in bilateral renal artery stenosis, they can reduce the resistance of the outflowing glomerular arterioles and, thereby, impair renal function. Β-blockers and calcium antagonists are also used.

Renin-secreting tumors

Reninsecreting tumors are extremely rare. They are usually hemangiopericytomas containing elements of juxtaglomerular cells. These tumors are detected on CT and are characterized by an increased level of renin in the venous blood of the affected kidney. Other renin-secreting neoplasms (for example, Wilms tumor, lung tumors), accompanied by secondary aldosteronism with arterial hypertension and hypokalemia, have also been described.

Accelerated arterial hypertension

Accelerated arterial hypertension is characterized by an acute and significant increase in diastolic pressure. It is based on progressive arteriosclerosis. Plasma renin and aldosterone concentrations can be very high. It is believed that hyperreninemia and accelerated development of arterial hypertension are caused by vasospasm and extensive sclerosis of the renal cortex. Intensive antihypertensive therapy usually relieves vasospasm and over time leads to a decrease in blood pressure.

Estrogen therapy

Estrogen replacement therapy or taking oral contraceptives may increase serum aldosterone concentrations. This is due to an increase in the production of angiotensinogen and, probably, angiotensin II. The level of aldosterone also increases secondarily, but hypokalemia with estrogen administration is rare.