Journal of Akhtar Saeed Medical & Dental College. JAMDC October – December 2020, Volume 02 Issue 04 www.amdc.edu.pk 205 Review Article RENIN – ANGIOTENSIN ALDOSTERONE SYSTEM (RAAS) Hamid Javaid Qureshi1 , Naila Hamid2 Abstract In the control of arterial blood pressure, fluid, and electrolyte balance, the renin-angiotensin-aldosterone system (RAAS) plays a very important role. Juxtaglomerular (JG) cells secrete renin which converts angiotensinogen to angiotensin 1 which is further changed into angiotensin II by angiotensin-converting enzyme (ACE) located in endothelial cells of the lung capillaries. Angiotensin II exerts its actions to regulate blood pressure, fluid, and electrolyte balance. Key Words: Renin, Angiotensinogen, Blood Pressure INTRODUCTION Renin-Angiotensin Aldosterone System (RAAS) is very important in the regulation of arterial blood pressure and fluid-electrolyte balance.1,2 Juxta Glomerular Cells (JG Cells) of the kidney are modified smooth muscle fibers present in the wall of afferent arterioles near the glomeruli.3-5 Renin is formed and stored in these cells. JG cells release renin into general circulation when arterial blood pressure falls. 6 Renin acts on a plasma protein angiotensinogen (synthesized in the liver) to form angiotensin I. 7,8 Renin circulates in the blood for 30 minutes to 1 hour and continues to form angiotensin I. 9 Circulating angiotensinogen is an alpha 2 globulin in the plasma. Its levels are increased by cortisol, thyroid hormones, estrogens, several cytokines and angiotensin II. 3 Angiotensin I has a mild vasoconstrictor activity. Angiotensin I is converted within a few seconds to minutes into angiotensin II (octapeptide) by the Angiotensin Converting Enzyme (ACE) present in endothelial cells of lungs capillaries.9,10 The kidney and blood vessels also contain this enzyme.8 (Figure-1) Juxtaglomerular cells are innervated by renal sympathetic nerves. When these cells are stimulated, there is release of renin.11 When blood pressure falls, glomerular filtration rate 1Professor Physiology, AMDC, Lahore. 2Professor Physiology, Al-Aleem Medical College, Lahore. decreases and concentration of NaCl at macula densa decreases. This causes the release of renin from JG cells.8 By regulating sodium balance and plasma volume and being potent vasocomtrictor, it contributes to the regulation of blood pressure.12,13 Figure-1. Renin-Angiotensin System9 Renin secretion is inversely proportional to NaCl concentration in distal renal tubules.2 Hamid Javaid Qureshi et al. Renin – Angiotensin aldosterone system (RAAS) JAMDC October – December 2020, Volume 02 Issue 04 www.amdc.edu.pk 206 Angiotensin II remains in the blood for 1-2 minutes as it is rapidly inhibiter by the enzyme angiotensinase present in blood and tissues.1 Angiotensin II receptors. In the human body, two types of angiotensin II receptors are present; AT1 and AT2. AT1 are further of 2 types. AT1A and AT1B. AT1A are present in blood vessel walls and brain and these mediate most of effects of angiotensin II. AT1B is found in anterior pituitary and adrenal cortex.14 An excess of angiotensin II down regulates vascular receptors (AT1A) and upregulates the adrenocortical receptors (AT1B).14-16 Physiological actions of Angiotensin II. Angiotensin II causes arteriolar vasoconstriction and a rise in arterial blood pressure. It is a 4-8 times more potent vasoconstrictor as compared to norepinephrine. Angiotensin II acts on zona glomerulosa of the adrenal cortex to release aldosterone. It is the major controller of aldosterone secretion. It facilitates release of nor-epinephrine from postganglionic sympathetic neurons and has a direct effect on renal tubules to increase Na+ reabsorption. It stimulates thirst center in the brain to increase water intake. It also increases secretion of vasopressin (ADH) from hypothalamo-neurohypophyseal system. These actions of angiotensin II increase Na+ and water reabsorption from renal tubules to increase blood pressure.1,3 Angiotensin III is also active in zona glomerulosa of adrenal cortex. Renin – angiotensin system has a role in maintaining normal blood pressure despite large variations in salt intake.1 Several signal pathways including Angiotensin II are known to trigger synthesis and degradation of collagen fibers in the heart leading to its remodeling, which may be manifested as cardiac dysfunction /cardiac failure.17 Inhibition of renin angiotensin aldosterone system Inhibitors of prostaglandin synthesis such as indomethacin and beta-adrenergic blockers such as propranolol reduce renin secretion. Pepstatin and enalkirem prevent conversion of angiotensinogens into angiotensin 1.18-21 Angiotensin-converting enzyme (ACE) inhibitors such as catapril and enalapril prevent the conversion of angiotensin 1 to angiotensin II.22,23 Saralasin is an analog of angiotensin II and is a competitive inhibitor of action of angiotensin II on both AT1 and AT2 receptors.24 Losartan (DUP – 753) selectively blocks AT1 receptors on vascular smooth muscle and adrenal cortex. 25-28 These drugs are used in the management of high blood pressure and heart failure.29 CONCLUSION The control of blood pressure, water and electrolyte balance involves renin angiotensin aldosterone system. AUTHOR’S CONTRIBUTION HJQ: Conception of idea and writing NH: Review critically REFERENCES 1. Hall JE. Nervous system urine concentration and dilution In: Guyton and Hall textbook of medical physiology 13th ed. India, ELSEVIER, 2016; 385-86. 2. Fountain JH, Lappin SL. Physiology, renin angiotensin system.9 May 2019. 3. 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