Rensin Aldosterone System

RAAS (Renin Angiotensin Aldosterone System) plays a role in the homeostatic process such as blood pressure and fluid volume control1. Renin is secreted in the blood from cells that are lining the glomeruli of the kidneys. The renin-secreting cells are sensitive to changes in blood flow and blood pressure. Angiotensinogen, a glycosylated protein that is primarily synthesized and secreted by the liver as well as other tissues is the sole precursor for angiotensin peptide. Renin catalyzes the conversion of a plasma protein called angiotensinogen into a decapeptide (consisting of 10 amino acids) called angiotensin I. An enzyme in the serum called angiotensin-converting enzyme (ACE) then converts angiotensin I into an octapeptide (consisting of

PLC activation is involved in the enhanced inositol triphosphate (IP3) and diacylglycerol. IP3 promotes the release of calcium from the intracellular sources and DAG (diacylglycerol) activates Protein Kinase C (PKC). Angiotensin II exhibits its function of vasoconstriction via AT1 receptor. ANG II also exerts functions like renal tubular salt absorption, stimulation of aldosterone release and also elicit effects like thirst and vasopressin secretion. Under certain Pathological conditions scientist have found that ANG II generated via renin system is involved in the promotion of vascular remodeling, cardiac hypertrophy remodeling and ECM deposition. Three different mechanisms are involved in the AT1 receptor regulation, transcription and modulation of activity of this receptor. AT2 receptor consist of 363 amino acids and molecular mass of 41 kDA. It is also a seven trans membrane receptor like AT1 receptor. If we evolutionary relationship is considered AT1 and AT2 are 34%

However, ANG (1-7) is the exception to this observation. ACE homolog ACE 2 is required for the generation of ANG (1-7) and G-Protein coupled Mas receptor. ANG (1-7) exhibits its effects through Mas receptor. This axis is having counter-regulatory effect to classical RAAS pathway. ANG (1-7) is a heptapeptide formed by monocarboxypeptidase which removes the amino acid from C-terminus of Ang I to form the biologically active peptide Ang (1-9), which is further cleaved to form Ang (1-7) through ACE and NEP (Neutral endopeptidase) hydrolysis reaction. In addition to this reaction Ang (1-7) can also directly formed from Ang II via cleavage of C-terminus Phenylalanine residue to form physiologically and biologically more relevant Ang (1-7). Discovery of Ang (1-7) antagonist A779, confirmed the existence of G-protein coupled Mas receptor for the function of Ang (1-7) and suggested that this peptide exerts its effects by binding to the receptor distinct from the AT1 and AT2 receptors. Researchers have confirmed that ANG (1-7)/ACE-2/Mas axis is likely acting as a counter-regulatory axis to counteract the deleterious effects of ACE/ANG II/ AT1 receptor axis. Ang (1-7) is subsequently metabolized into the Ang (1-5) by ACE and ACE2 is capable of further metabolizing peptides like