Introduction of Renin-Angiotensin-Aldosterone System (RAAS)

The human body is composed of different types of system that are associated with each other. The Renin-Angiotensin-Aldosterone System (RAAS) is one of the most major systems for survival. In 1988, renin was discovered by Tiegerstedt and Bergman, since then extensive research has been carried out to unravel the RAAS and its association with pathophysiology of various diseases. RAAS is responsible for proper functioning of vital organs such as heart and kidney and prevents extreme fluctuations. However, any damage to this system can initiate irregularities in blood pressure that may lead to acute or chronic illness or in severe cases it may result into sudden death. Renin and angiotensin are important components of RAAS, in which renin is secreted by kidney granular cells. Prorenin is a precursor of renin, it is a 406 amino acid protein which gets activated after processing. Prorenin is activated by proteolytical and non-proteolytical processes. Moreover, in proteolytical process, prorenin is activated in kidney with the help of neuroendocrine convertase enzyme 1 or cathepsin. Through non-proteolytical methods, prorenin is activated in various organs by prorenin/renin receptor. Expression of renin is increased by low blood sodium level, low blood pressure, activation of sympathetic nervous system. Renin converts α-2-globulin protein angiotensinogen to angiotensin I by starting the bond between leucine and valine. The level of angiotensinogen in plasma is increased by thyroid hormones, estrogen, corticosteroids. Angiotensin-I is converted to angiotensin II in the capillaries of lungs, kidney epithelial cells and endothelial cells by angiotensin converting enzyme (ACE). Angiotensin II constricts smooth muscles thus it has vasoactive effect on blood vessels. Therefore, it results in increased heart pulse rate, blood pressure. Angiotensin II stimulates plasminogen activator inhibitors PAI-1 and PA-2, adrenal cortex to secrete aldosterone. Aldosterone stimulates proximal tubules of kidney to facilitate sodium reabsorption thus regulating sodium-potassium homeostasis [1, 2]. Some factors are responsible for RAAS modulation such as pregnancy, birth control pills, anti-hypertensive agent, vasodilators, hormones (cortisol, thyroid, testosterone, and estrogen), and diuretics. Some tumors such as renin secreting tumors of the juxta-glomerular cell, renal cell carcinoma and Wilms’s tumor can raise renin levels [3].