Angiotensin: hormone synthesis, functions, receptor blockers
The content of the article:
- Synthesis of angiotensin
- Renin-angiotensin-aldosterone system
- Elevated angiotensin levels
- Angiotensin 2 blockers
Angiotensin is a peptide hormone that causes narrowing of blood vessels (vasoconstriction), high blood pressure, and the release of aldosterone from the adrenal cortex into the bloodstream.
Angiotensin increases blood pressure by narrowing the blood vessels
Angiotensin plays a significant role in the renin-angiotensin-aldosterone system, which is the main target of blood pressure lowering drugs.
The level of angiotensin in the blood rises with renal hypertension and renin-producing neoplasms of the kidneys, and decreases with dehydration, Conn's syndrome and removal of the kidney.
Synthesis of angiotensin
The precursor of angiotensin is angiotensinogen - a protein of the globulin class, which belongs to serpins and is produced mainly by the liver.
The production of angiotensin 1 occurs under the influence of renin on the angiotensinogen. Renin is a proteolytic enzyme that belongs to the most significant renal factors involved in the regulation of blood pressure, while it itself does not possess pressor properties. Angiotensin 1 also lacks vasopressor activity and is rapidly converted to angiotensin 2, which is the most potent of all known pressor factors. The conversion of angiotensin 1 to angiotensin 2 occurs due to the removal of C-terminal residues under the influence of an angiotensin-converting enzyme, which is present in all tissues of the body, but is most synthesized in the lungs. The subsequent cleavage of angiotensin 2 leads to the formation of angiotensin 3 and angiotensin 4.
In addition, the ability to form angiotensin 2 from angiotensin 1 is possessed by tonin, chymases, cathepsin G and other serine proteases, which is the so-called alternative pathway of angiotensin 2 formation.
Renin-angiotensin-aldosterone system
The renin-angiotensin-aldosterone system is a hormonal system that regulates blood pressure and blood volume in the body.
The renin-angiotensin-aldosterone cascade begins with the synthesis of preprorenin by translation of renin mRNA in the juxtaglomerular cells of the afferent arterioles of the kidneys, where prorenin is formed from preprorenin. A significant part of the latter is released into the bloodstream by exocytosis, but part of prorenin is converted into renin in the secretory granules of juxtaglomerular cells, then also being released into the bloodstream. For this reason, the normal volume of prorenin circulating in the blood is much higher than the concentration of active renin. Control of renin production is a determining factor in the activity of the renin-angiotensin-aldosterone system.
Renin regulates the synthesis of angiotensin 1, which has no biological activity and acts as a precursor of angiotensin 2, which is a strong direct vasoconstrictor. Under its influence, there is a narrowing of blood vessels and a subsequent increase in blood pressure. It also has a prothrombotic effect - it regulates platelet adhesion and aggregation. In addition, angiotensin 2 potentiates the release of norepinephrine, increases the production of adrenocorticotropic hormone and antidiuretic hormone, and can induce thirst. By increasing the pressure in the kidneys and narrowing the efferent arterioles, angiotensin 2 increases the rate of glomerular filtration.
The task of the renin-angiotensin-aldosterone system is the regulation of blood pressure
Angiotensin 2 exerts its effect on the cells of the body through angiotensin receptors (AT receptors) of various types. Angiotensin 2 has the greatest affinity for AT 1 receptors, which are localized mainly in the smooth muscles of blood vessels, the heart, some areas of the brain, liver, kidneys, and adrenal cortex. The half-life of angiotensin 2 is 12 minutes. Angiotensin 3, formed from angiotensin 2, has 40% of its activity. The half-life of angiotensin 3 in the bloodstream is approximately 30 seconds, in body tissues - 15-30 minutes. Angiotensin 4 is a hexopeptide and is similar in properties to angiotensin 3.
Angiotensin 2 and the extracellular level of potassium ions are among the most important regulators of aldosterone, which is an important regulator of potassium and sodium balance in the body and plays a significant role in the control of fluid volume. It increases the reabsorption of water and sodium in the distal convoluted tubules, collecting ducts, salivary and sweat glands, and the large intestine, causing the excretion of potassium and hydrogen ions. An increased concentration of aldosterone in the blood leads to a delay in the body of sodium and increased excretion of potassium in the urine, that is, to a decrease in the level of this trace element in the blood serum (hypokalemia).
Elevated angiotensin levels
With a prolonged increase in the concentration of angiotensin 2 in the blood and tissues, the formation of collagen fibers increases and hypertrophy of smooth muscle cells of blood vessels develops. As a result, the walls of blood vessels thicken, their inner diameter decreases, which leads to an increase in blood pressure. In addition, depletion and degeneration of heart muscle cells occurs, followed by their death and replacement by connective tissue, which is the cause of the development of heart failure.
Prolonged spasm and hypertrophy of the muscular layer of the blood vessels cause deterioration of the blood supply to organs and tissues, primarily the brain, heart, kidneys, and visual analyzer. A prolonged lack of blood supply to the kidneys leads to their dystrophy, nephrosclerosis and the formation of renal failure. With insufficient blood supply to the brain, sleep disturbances, emotional disturbances, decreased intelligence, memory, tinnitus, headache, dizziness, etc. are observed. Heart ischemia can be complicated by angina pectoris, myocardial infarction. Insufficient blood supply to the retina leads to a progressive decrease in visual acuity.
A prolonged increase in the concentration of angiotensin 2 leads to a decrease in the sensitivity of cells to insulin with a high risk of developing type 2 diabetes mellitus.
Angiotensin 2 blockers
Angiotensin 2 blockers (angiotensin 2 antagonists) are a group of medicines that lower blood pressure.
Medicines that act by blocking angiotensin receptors have been developed in the course of studying angiotensin 2 inhibitors, which are able to block its formation or action and thus reduce the activity of the renin-angiotensin-aldosterone system. These substances include rhinin synthesis inhibitors, angiotensinogen formation inhibitors, angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, etc.
Angiotensin 2 receptor blockers (antagonists) are a group of antihypertensive drugs that combine drugs that modulate the functioning of the renin-angiotensin-aldosterone system through interaction with angiotensin receptors.
Angiotensin blockers are used to lower blood pressure
The main mechanism of action of angiotensin 2 receptor antagonists is associated with the blockade of AT 1 receptors, thereby eliminating the adverse effect of angiotensin 2 on vascular tone and normalizing high blood pressure. Taking drugs of this group provides a long-term antihypertensive and organoprotective effect.
Currently, clinical studies are ongoing to study the effectiveness and safety of angiotensin 2 receptor blockers.
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Anna Aksenova Medical journalist About the author
Education: 2004-2007 "First Kiev Medical College" specialty "Laboratory Diagnostics".
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