VPT 321: Veterinary Neuropharmacology (2+1)

Generation and degradation of angiotensin

GENERATION AND DEGRADATION OF ANGIOTENSINS

• Angiotension II is a octapeptide generated in the plasma from plasma alpha globulin involved in electrolyte, blood volume and pressure homeostasis.
• Enzyme renin is responsible for the pressor effects, later it became evident that the angiotensin converting enzyme (ACE) which is responsible for the formation of inactive fragments of Angiotensin I to Angiotensin II  (potent vasoconstrictor) has paved the way for development of prototype ACE inhibitor Eg: Captopril.
• Renin is the limiting factor for Angiotensin II generation.
• Plasma half life of renin is 15 minutes
• Biological potency of Angiotensin I is very short,  hence it is rapidly converted into Angiotensin II by ACE a dipeptidyl carboxypeptidase located primarily on the luminal surface of vascular endothelial cells in lungs.
• Angiotensin II has a very short half life (less than a minute)
• Angiotensin III is less potent and stimulate aldosterone secretion
• Angiotensin III is acted on by angiotensinases to inactive metabolites.
• Blood vessels contain circulating renin, angiotensinases and produce Angiotensin II within their wall.
• Locally renin-angiotensin system present in heart, blood vessels, brain, kidneys, adrenals generate Angiotensin II and operate locally.