CLINICAL IMPLICATIONS OF RENIN-ANGIOTENSIN SYESTEM IN MAMMALS

Renin is a proteolytic enzyme that is primarily produced by the juxtaglomerular cells of the kidney that is encoded by the REN gene. Angiotensin (Ang) II is locally produced in the kidney. The Angiotensin II is an active peptide and it constricts the blood vessels due to which blood pressure increases. The renin-angiotensin system altogether acts as a hormonal system in regulating the blood pressure and water or osmotic balance of the system. The renin-angiotensin system in collaboration with aldosterone is known as the Renin-angiotensin aldosterone system as it regulates various activities in the body and its function as a hormone system. There are many clinical implications of the renin-angiotensin system, some of them are documented in this review, that include controlling hypertension and stress, chronic kidney diseases, cardiovascular diseases, central nervous system disorders and memory facilitation. _____________________________________________________________________________ INTRODUCTION Renin is a proteolytic enzyme that is primarily produced by the juxtaglomerular cells of the kidney that is encoded by the REN gene which is present on chromosome 1q32.Apart from kidney it also occurs in other organs e.g. in brain where it is associated in the control of numerous activities (Auronet al., 2014). It is also the enzyme that is involved in the catalysis, in the first step of the activation pathway of angiotensinogen to angiotensin I, and gene mutation in it is related to renal tubular dysgenesis, hyperproreninemia and hyperuricemic nephropathy. Angiotensin (Ang) II is locally produced in the kidney by awell-established method, any local effects of this locally produced Ang-II and any interference in this process is supposed to trigger significant renal effects of the blockers of renin-angiotensin system which is also abbreviated to as RAS (Matsusakaet al., 2012). Recent studies revealed that the useof infusions of 125Ilabelled angiotensins at renal tissue sites allowsconsiderable uptake of the circulating 125I-Ang II thus helping in the detection of 125I-Ang at points that considerably do not affect the blood pressure the tissue levels at steady-stateparalleled to the steady-state plasma levels, approximately four to five times, of 125I-Ang II. Thus the renin-angiotensin system altogether acts as a hormonal system in regulating the blood pressure and water or osmotic balance of the system (Cousin et al., 2009). The renin-angiotensin system in collaboration with aldosterone is also referred to as the Renin-angiotensin aldosterone system abbreviated as RAAS, due to its regulation of various activities in the body and its function as a hormone system. IJARR, 1(2), 2016; 71-83 72 Mechanism of action of Renin-Angiotensin Aldosterone System During the shortage of the renal blood supply, the juxtaglomerular cells of the kidney activates the prorenin receptor which secretes the renin directly into the blood circulation (Jeunemaitre, 2008). The renin of the plasma then brings about the conversion of Angiotensinogen (from liver) to Angiotensin I (Bader et al., 2012). The conversion of Angiotensin I to Angiotensin II then takes place with the aid of an enzyme i.e. Angiotensin-converting enzyme referred to as ACE, this enzyme is produced in the lungs (Demurtaset al.& Lu et al., 2013). The Angiotensin II is an active peptide and it constricts the blood vessels due to which blood pressure increases. The stimulus from Angiotensin II brings about the secretion of the aldosterone hormone from the adrenal cortex, which further increases the blood pressure, as it causes the increase in the reabsorption of sodium and water in the blood by the kidney tubules. Fig. 1.The renin-angiotensin aldosterone system (Macia-Heras et al., 2012). Clinical implications There aremany clinical implications of the renin-angiotensin system in the body. There is a clear-cut evidence of this showing an important role for the tissue angiotensin systems in the indication of cardiovascular diseases and also in their structural remodelling (Auronet al., 2014). The synthesis of aldosterone regulated by cardiac tissue is a well-known example of a reninaldosterone system existence in the heart. Moreover many of these have therapeutic implications, and also more specifically the blockers of the angiotensin receptors as well as the inhibitors of the angiotensin convertingenzyme. IJARR, 1(2), 2016; 71-83 73 Table 1: Role of Renin-Angiotensin system in clinical disorders (Wright et al., 2013). Clinical disorder Treatment Strategy Response Bibliography Cerebroprotection AngIV administered to rats and gerbils Facilitated cerebral blood flow and protected against ischemia Faure et al.,(2006) Depression ACE inhibitors administered to AD patients Reduced depressive symptoms Isingriniet al.,(2009) Diabetes ARBs administered to type 1 diabetic patients Protected against end organ damage Chen et al.,(2008) Memory facilitation AT4 receptor agonist in rats Facilitated long-term potentiation Improved spatial memory Davis et al.,(2006) Stress Candesartan blockade of AT1 receptorsin rats Prevented AT1 receptor binding in anterior pituitary, adrenal and PVN, also reduced elevations of pituitary ACTH and adrenal corticosterone Nishimura et