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Renin-Angiotensin-Aldosterone System Juxtaglomerular apparatus secretes renin. Renin acts on angiotensinogen (gamma globulin from the liver) giving angiotensin I Angiotensin converting enzyme (ACE) acts on angiotensin I giving angiotensin II 1. 2. 3. Renin-Angiotensin-Aldosterone System Renin: It is secreted by the juxtaglomerular cells in Kidney Changes in secretion is in response to changes in renal arterial pressure, sympathetic nervous system signals and some hormones Its substrate is angiotensinogen Renin-Angiotensin-Aldosterone System Angiotensinogen It is a glycoprotein synthesized and secreted into the bloodstream by the liver Angiotensinogen Renin angiotensin I ACE Angiotensin III Angiotensin II Renin-Angiotensin-Aldosterone System Angiotensin converting enzyme (ACE) is also known as kinanase II It converts angiotensin I to II (vasoconstrictor) and inactivates bradykinin (vasodilator) The principal site of its action is vascular epithelium It is inhibited by synthetically produced Captopril drug Renin-Angiotensin-Aldosterone System Angiotensin II 1. Stimulates aldosterone production 2. Stimulates ADH secretion from pituitary 3. Highly potent vasoconstrictor 4. Stimulates thirst 5. Stimulates release of catecholamines by adrenal medulla Angiotensin III Stmulates aldosterone production without vasoconstriction Role of Angiotensin II Hypertensive Angiotensin ll is a powerful vasoconstrictor. It constricts the blood vessels and raises the peripheral resistance, thereby acting to restore blood pressure. Angiotensin ll also increases the secretion of aldosterone leading to Na+ reabsorption. Effects of Angiotensin II Renin-Angiotensin-Aldosterone System Aldosterone: It is a mineralocorticoid produced in the adrenal cortex Increases cortical collecting tubule reabsorption of Na+ and secretion of K+ and H+ Regulation of Aldosterone Angiotensin II and III stimulate aldosterone release Changes in volume ( long Negative feedback loop) Inhibition of renin secretion by angiotensin II (short negative feedback loop) Endothelin and vasopressin stimulate aldosterone secretion ANP is a potent inhibitor, dopamine also inhibits it. Endothelin ADH Blood Volume Osmolarity Kidney ANP Aldosterone Distal Tubules Na & H2O Angiotensin III JGA Renin Angiotensin II Aldosterone Hypertensive Stimulates Na+ reabsorption and K+ excretion Aldosterone-mediated responses in the Kidney Renin-Angiotensin-Aldosterone System High Na intake suppresses the system Acute decrease in Na activates RAS which in turn stimulates aldosterone, leading to Na retention by kidneys. Prolonged Na restriction increases sensitivity of adrenal to angiotensin ( aldosterone) and decreases sensitivity of vasculature.