Renin-Angiotensin System

The renin-angiotensin system (RAS) is a hormone system that regulates blood pressure and water balance.

The kidneys produce renin when the blood volume is low. Renin stimulates the production of angiotensin. Angiotensin causes blood vessels to constrict, resulting in increased blood pressure. Angiotensin also stimulates the secretion of the hormone aldosterone from the adrenal cortex. Aldosterone causes the tubules of the kidneys to increase the reabsorption of sodium and water. This increases the volume of fluid in the body, which also increases blood pressure.

The system can be activated when there is a loss of blood volume or a drop in blood pressure (such as in hemorrhage). If the perfusion of the juxtaglomerular apparatus in the kidney's macula densa decreases, then the juxtaglomerular cells release the enzyme renin. Renin cleaves a zymogen, an inactive peptide, called angiotensinogen, converting it into angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin-converting enzyme (ACE) which is found mainly in lung capillaries. Angiotensin II is the major bioactive product of the renin-angiotensin system, binding to receptors on intraglomerular mesangial cells, causing these cells to contract along with the blood vessels surrounding them and causing the release of aldosterone from the zona glomerulosa in the adrenal cortex. Angiotensin II acts as an endocrine, autocrine/paracrine, and intracrine hormone. Patil Jaspal et al. have shown local synthesis of Angiotensin III in neurons of sympathetic ganglia.

If the renin-angiotensin-aldosterone system is too active, blood pressure will be too high. There are many drugs that interrupt different steps in this system to lower blood pressure. These drugs are one of the main ways to control high blood pressure (hypertension), heart failure, kidney failure, and harmful effects of diabetes.