VPT 321: Veterinary Neuropharmacology (2+1)

ANGIOTENSIN RECEPTORS

 Angiotensin receptors (AT) are present on the surface of target cells.

• Two subtype  receptors AT₁ and AT₂ have been identified.
• Losartan is the specific antagonist for AT₁ receptor.
• All the effects of Angiotensin II are mediated through AT₁ receptors.
•  AT₂ receptors have been identified in adrenal medulla and CNS
• AT₁ receptor is a G-protein coupled receptor utilizing different transducer mechanism in different tissues.
•  Phospholipase C - IP3/DAG and intracellular calcium ions release underlies vascular and visceral smooth muscle contraction by activating myosin light chain kinase.
• Membrane calcium ions are also activated.
• Calcium movement induces aldosterone synthesis release, cardiac inotropy,depolarization of autonomic ganglia, adrenal medulla resulting catecholamine release and sympathetic outflow.
• DAG activates protein kinase C which phosphorylase intracellular proteins and promotes cell growth.
• In liver and kidney Angiotensin II inhibits adenyl cyclase.
• Intrarenal homeostatic mechanism involves prostaglandin and leukotrienes production through activation of phospholipase A₂.
• This molecular mechanism has a wide effect on myocardium, vascular smooth muscle, fibroblasts through AT₁ receptor where Angiotensin II has sustained effect on cell growth and intracellular matrix synthesis.