Cardiac production of angiotensin II and its pharmacologic inhibition: effects on the coronary circulation.
Angiotensin II (AII), produced systemically as well as locally in the heart, affects the coronary circulation, as do consequences of its pharmacologic inhibition. AII is a powerful vasoconstrictor directly acting on vascular smooth muscle cells, modulating sympathetic innervation and calcium ion influx, and releasing other vasoconstrictor factors. In addition to these immediate actions, AII has longer-term biologic actions that influence cardiac endothelial function, vascular smooth muscle cell phenotype expression, and fibroblast proliferation. Moreover, the production of AII is interrelated with the vasodilator substances bradykinin, nitric oxide, and prostaglandins E2 and I2 (prostacyclin). Circulating hormonal actions of AII include fluid retention, direct vasoconstriction, and sympathetic neuromodulation, all resulting in increased left ventricular preload and afterload. Because of these local and hormonal characteristics, AII can immediately affect the myocardial balance of metabolic demand and supply and long term can induce structural vascular and myocardial alterations. Pharmacologic inhibition of AII production likely conveys myocardial and vascular protection in situations of acute myocardial oxygen debt. In the long term, inhibition of AII may attenuate structural changes in the coronary microcirculation related to various cardiomyopathies or acute tissue injury, and direct antiatherogenic effects may also occur.
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D003324:Coronary Artery Disease / Q000378:metabolism / Q000517:prevention & control; D003326:Coronary Circulation / Q000187:drug effects*; D006801:Humans; D017202:Myocardial Ischemia / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism