System renin-angiotensin-aldosterone

The system renin-angiotensin-aldosterone ( RAA ) is a cascade of regulation endocrinienne and enzymatic. It is a hormonal system which one finds in the Rein and which is used to preserve the Homéostasie hydrosodée (balance between the Na+ ions and water).

Operation

The Angiotensinogène, inactive protein produced by the liver, circulates in blood. It is the precursor of active peptides, and the only substrate of the renin. Other proteases (cathepsine G, kallicréine tissue) can degrade angiotensinogene and allow the active peptide release.

In the event of fall of the pressure in the renal Artère (there exists other stimuli: lower Natrémie on the level of the distal circumvented tube and stimulation of the juxta-glomerular cells by the Système beta-adrenergic), the Rénine (a Enzyme sometimes regarded as a Hormone) is secreted by the Rein. The Angiotensinogène, secreted by the liver, is cleaved by the renin to give a décapeptide called Angiotensine I , inactive. The Angiotensine I will be then transformed into Angiotensine II mainly on the level of the lung by the Enzyme of conversion of the angiotensin (ACE) which is a carboxypeptidase. The Angiotensine acts by setting on its receiving transmembrane (of which there exist two types AT1 and AT2 which have sometimes antagonistic roles). Via receiver AT1, it supports the rise in the blood Pressure by various mechanisms:

stimulation of the Vasoconstriction of the Artériole S, which causes an increase in peripheral resistances, as well as a maintenance of glomerular filtration.
stimulation of the secretion of Aldosterone, a Hormone secreted by the glands Suprarenal S which causes an increase in the Volémie by reabsorption of Sodium (Na) and of water on the level of the Rein S (in the tubule proximal and the collecting channel).
stimulation of the secretion of Vasopressine (still called antidiuretic hormone) which limits the water loss in the urines.
stimulation of the feeling of thirst, involving a greater absorption of water which mechanically will increase blood volume and thus the blood pressure.

The Enzyme of conversion of the angiotensin also acts on the system kallikréine/kinine by inactivant the Bradykinine. This enzyme stimulates the vasoconstriction by generating the Angiotensine II (Peptide vasoconstrictor) and by inactivant the Bradykinine (peptide vasodilator).

To stop the effects of angiotensin II, its secretion should be stopped. This takes place through two rétrocontrôles negative. Firstly, angiotensin II has an inhibiting effect on secretion of renin, i.e., plus the angiotensin II concentration increases, plus the concentration in renin decreases. Thus there is less and less formed angiotensin II. The negative second rétrocontrôle is due to the action of the Aldostérone, in particular by the regulation of the expression of the epithelial Canal to sodium or ENaC and of the Na/K ATPase in the distal tube of the kidney involving a water and sodium retention, therefore of blood pressure. The increase in the blood pressure on the level of the apparatus juxtaglomérulaire of the kidney strongly will inhibit the secretion of renin.

Many a Médicament S Antihypertenseur S blocks this cascade of reactions at various levels cause a drop in the blood Pressure:

Inhibiting of the Enzyme of conversion of the angiotensin (captopril, enalapril, ramipril)
Blockers of receiver AT1 (valsartan, losartan, telmisartan, candesartan)
Diurétiques

An inhibiter of the renin, the aliskiren, was put on the market in March 2007.

The SRAA also contributes to the homeostasis of potassium (Kaliémie) via the action of the aldosterone on the pump Na/K ATPase.

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