The complex rennin-angiotensin system governs the regulation of arterial pressure, that is, the force exerted by the blood on the walls of the arteries, on which the adequate perfusion of blood to all parts of the body depends; this pressure is influenced, among other things, by amount of blood that the heart pushes when it pumps, by its force of contraction and by the resistances that oppose the free flow of the blood stream. Well, the renin-angiotensin system acts on the one hand by increasing blood volume (by stimulating the synthesis and release of aldosterone from the adrenal cortex), and on the other by inducing vasoconstriction.
Vasoconstriction - that is, the decrease in the lumen of blood vessels - induced by the renin-angiotensin system significantly increases blood pressure. We become aware of this phenomenon when watering the garden with a rubber hose we reduce its caliber with our fingers to increase the distance reached by the jet of water. Equally intuitive is the fact that this, and with it the water pressure, increases and decreases as we open or close the tap, respectively. The same effect is induced by "aldosterone, a hormone synthesized by the adrenal cortex under the stimulus of the renin-angiotensin system. In fact, aldosterone acts on the distal part of the nephrons (functional units of the kidney), where it causes a decrease in sodium excretion. and water, and an increase in the excretion of potassium and hydrogen ions. The kidney's retention of sodium and water increases plasma volume and blood pressure, just like in the example of water and tap.
The primary control center of the renin-angiotensin system is found in the kidney, and more precisely in the cells of the juxtaglomerular apparatus, where the proteolytic hormone renin is produced and stored. Its biological effect leads it to act on a plasma protein synthesized by the liver, called angiotensinogen, transforming it into the decapeptide angiotensin I. This blood protein is in turn transformed by a conversion enzyme (the so-called ACE, acronym for Angiotensin Converting Enzyme) in the octapeptide angiotensin II, which undergoes a further enzymatic lysis to transform itself into angiotensin III and other metabolites, such as angiotensin IV and angiotensin 1,7.
Angiotensin III, to a lesser extent angiotensin I, and in particular angiotensin II (which represents the most powerful vasoconstrictor of our organism), are responsible for the aforementioned biological effects of the renin-angiotensin system, which they perform through interaction with specific receptors (AT1 and AT2). Among the two, the most represented are AT1, which when stimulated by the ligand:
- they favor the contraction of the smooth muscle of the arterioles and of the striated muscle of the myocardium (positive inotropic effect).
- they stimulate the thirst center and the production of aldosterone, favoring the reabsorption of sodium and increasing the volume (which also increase directly acting at the level of the renal tubule, with action similar to aldosterone itself and to ADH).
The AT2 receptors are more represented in the fetal tissues, they progressively decrease in the newborn and although having an effect that is still uncertain, they seem to play a role in tissue development.
The renin-angiotensin system is therefore activated whenever conditions occur in an acute way that lead to a significant drop in blood pressure, for example a trauma with blood loss. The half-life of renin - which is degraded in the liver - is in fact short, in the order of 10-20 minutes; the same goes for angiotensin II, which is rapidly destroyed in the peripheral capillary beds by numerous enzymes called angiotensinases. Angiotensinogen, on the other hand, is normally present at high levels in plasma and has a prolonged half-life.
Drugs active on the renin-angiotensin system
Angiotensin II receptor antagonists
- Losartan
- Telmisartan
- Irbesartan
- Olmesartan
- Valsartan
ACE Inhibitors
- Benazepril (Cibacen®)
- Captopril (Lopirin®, Tensobon®, many generics)
- Cilazapril (Dynorm®)
- Enalapril (Xanef®, Pres®, many generics)
- Fosinopril (Fosinorm®, Dynacil®)
- Imidapril (Tanatril®)
- Lisinopril (Acerbon®, Coric®, generics)
- Moexipril (Fempress®)
- Perindopril (Coversum®, Preterax®, generic)
- Quinapril (Accupro®, generic)
- Ramipril (Delix®, Vesdil®, Triatec®, generics)
- Spirapril (Quadropril®)
- Trandolapril (Gopten®, Udrik®)
Regulation of the renin angiotensin system "
