DefinitionThis section has been translated automatically.
The renin-angiotensin-aldosterone system is a phylogenetic old humoral system that primarily serves to control the electrolyte and fluid balance and the blood pressure of the organism.
The central protease renin acts as an enzyme that cleaves the decapeptide angiotensin I from the N-terminal end of the angiotensinogen (an alpha-globulin of hepatic origin).
General informationThis section has been translated automatically.
Renin itself is produced in the so-called juxtaglomerular cells (JK cells, pole cushion cells) in the wall of the vas afferens of a glomerule of prorenin by splitting off a 43 amino acid long prosegment and stored in vesicles. Renin is released via exocytosis and can be detected in the blood.
Angiotensin-I is finally cleaved by the enzymatic activity of the angiotensin converting enzyme (ACE) into the active angiotensin II (A II) by splitting off two terminal amino acids.
Angiotensin II is a small peptide consisting of only 8 amino acids. It exerts a whole range of effects on the cardiovascular system which serve to maintain blood pressure or blood volume.
ACE is a non-specific carboxypeptidase, which contains a Zn2+ in the catalytic centre. ACE is produced in the endothelial cells of the vessels and in the lungs. Besides the formation of the strong vasocontrictor A II, ACE also catalyzes the degradation of the strong vasodilator bradykinin.
The serine proteases chymase and cathepsin G also provide alternative, ACE-independent pathways of A II formation. Both enzymes catalyze the local formation of angiotensin-II in the heart and kidneys.
Angiotensin-II occurs in the lungs in the highest concentration. A-II also binds to receptors of cells of the zona glomerulosa of the adrenal cortex, where it causes the formation and release of aldosterone. A-II is broken down by aminopeptidases and disappears very quickly from the circulation (HRT: 30-60 s).
An excessive systemic or local release of angiotensin-II has damaging and far-reaching effects on the endothelium. This may be a major pathophysiological mechanism in the development of hypertension.
PathophysiologyThis section has been translated automatically.
Regulation of renin release: Currently 5 mechanisms of renin release are known:
- Baroreceptor mechanism
- Macula densa mechanism
- Beta1 receptor mediated mechanism
- AT1 receptor-mediated mechanism
- cGMP-mediated mechanism
Baroreceptor mechanism: The release of renin is inversely proportional to the level of perfusion pressure in the vas afferens of the glomeruli. The higher the perfusion pressure, the lower the renin release. It can be assumed that the perfusion pressure influences the JG cells via COX-2 mediated local formation of PGE2. In these cells an increase in the cAMP concentration occurs, which causes renin release.
Macula densa mechanism: The epithelial cells of the macula densa register the luminal NaCL or CL- concentration in the distal tubule via the activity of their Na+/K+/2CL- importer, which transports NaCl and KCl into the epithelial cells. At a low transport rate the renin release increases and at a high transport rate it decreases.
Beta1 receptor mechanism: these are expressed by the JG cells. These receptor pores are excited by the activity of the sympathetic nervous system and mediate an increase in renin release.
AT1 receptor mechanism: Renin release is inhibited by activation of AT1 receptors (activation by A II) expressed by JG cells.
CGMP-mediated mechanism: The activation of AT2 receptors or the activation of natriuretic peptides on JG cells increases the cGMP concentration in these cells and leads to an inhibition of renin release.
In Liddle syndrome, the cause of hypertension is a genetic defect encoding the beta and gamma subunits of the epithelial sodium channel. The mutation results in an activated Na channel and increased reabsorption of sodium in the distal tubule, which is the cause of hypertension.
LiteratureThis section has been translated automatically.
- Graefe KH et al. sympathetic nervous system. In: Graefe KH et al (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart p.165
- Graefe KH et al. heart failure. In: Graefe KH et al (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart S.513