The renin-angiotensin-aldosterone system (RAAS) comprises renin, angiotensin II (ANG II) and aldosterone. These compounds interact through a sequence of biochemical events (1).
Renin is an aspartyl protease that triggers the first step in the RAAS activation. It is primarily secreted into the bloodstream by the kidneys in response to reduced blood pressure. Renin specifically acts on the substrate angiotensinogen, cleaving it into the decapeptide angiotensin I (ANG I). Angiotensin-converting enzyme (ACE) then converts ANG I into the octapeptide ANG II (2).
ANG II is a vasoactive peptide primarily responsible for fluid and electrolyte levels, aldosterone production and other physiological functions. It exerts its actions through G-protein coupled receptors, ANG II Type 1 Receptor (AT1-R) and ANG II Type 2 Receptor (AT2-R) (1).
Aldosterone acts on the kidneys to maintain electrolyte and fluid homeostasis by binding to the mineralocorticoid receptor (MR) on the principal cell of the kidney collecting duct.
The RAAS regulates blood pressure, fluid and electrolyte balance, vasoconstriction, cardiac output, cell growth, angiogenesis and vascular integrity, among other physiological functions. Dysregulation of the RAAS has been implicated in the pathophysiological events associated with hypertension, cardiovascular diseases and kidney diseases (3).