1. Renin-Angiotensin-Aldosterone System Juxtaglomerular apparatus secretes renin. Juxtaglomerular apparatus secretes renin. Renin acts on angiotensinogen (gamma globulin from the liver) giving angiotensin I Renin acts on angiotensinogen (gamma globulin from the liver) giving angiotensin I Angiotensin converting enzyme (ACE) acts on angiotensin I giving angiotensin II Angiotensin converting enzyme (ACE) acts on angiotensin I giving angiotensin II

2. Renin-Angiotensin-Aldosterone System Renin: Renin: 1. It is secreted by the juxtaglomerular cells in Kidney 2. Changes in secretion is in response to changes in renal arterial pressure, sympathetic nervous system signals and some hormones 3. Its substrate is angiotensinogen

3. Renin-Angiotensin-Aldosterone System Angiotensinogen Angiotensinogen It is a glycoprotein synthesized and secreted into the bloodstream by the liver Angiotensinogen Renin angiotensin I Angiotensinogen Renin angiotensin I ACE ACE Angiotensin III Angiotensin II

4. Renin-Angiotensin-Aldosterone System Angiotensin converting enzyme (ACE) is also known as kinanase II Angiotensin converting enzyme (ACE) is also known as kinanase II It converts angiotensin I to II (vasoconstrictor) and inactivates bradykinin (vasodilator) It converts angiotensin I to II (vasoconstrictor) and inactivates bradykinin (vasodilator) The principal site of its action is vascular epithelium The principal site of its action is vascular epithelium It is inhibited by synthetically produced Captopril drug It is inhibited by synthetically produced Captopril drug

5. Renin-Angiotensin-Aldosterone System Angiotensin II 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 Angiotensin III Stmulates aldosterone production without vasoconstriction

6. 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 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. Angiotensin ll also increases the secretion of aldosterone leading to Na+ reabsorption.

7. Effects of Angiotensin II

8. Renin-Angiotensin-Aldosterone System Aldosterone: Aldosterone: It is a mineralocorticoid produced in the adrenal cortex Increases cortical collecting tubule reabsorption of Na + and secretion of K + and H +

9. Regulation of Aldosterone Angiotensin II and III stimulate aldosterone release Angiotensin II and III stimulate aldosterone release Changes in volume ( long Negative feedback loop) Changes in volume ( long Negative feedback loop) Inhibition of renin secretion by angiotensin II (short negative feedback loop) Inhibition of renin secretion by angiotensin II (short negative feedback loop) Endothelin and vasopressin stimulate aldosterone secretion Endothelin and vasopressin stimulate aldosterone secretion ANP is a potent inhibitor, dopamine also inhibits it. ANP is a potent inhibitor, dopamine also inhibits it.

10. Aldosterone Angiotensin II Angiotensin III Endothelin ADH Kidney Renin JGA Distal Tubules Blood Volume Na & H2O ANP Osmolarity

11. Aldosterone Hypertensive Stimulates Na + reabsorption and K + excretion Stimulates Na + reabsorption and K + excretion

12. Aldosterone-mediated responses in the Kidney

17. Renin-Angiotensin-Aldosterone System High Na intake suppresses the system High Na intake suppresses the system Acute decrease in Na activates RAS which in turn stimulates aldosterone, leading to Na retention by kidneys. 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. Prolonged Na restriction increases sensitivity of adrenal to angiotensin ( aldosterone) and decreases sensitivity of vasculature.