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 inf lux, and releasing other vasoconstrictor factors. In addition to these imme diate 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 An is interrelated w ith the vasodilator substances bradykinin, nitric oxide, and prostaglandins E-2 and I-2 (prostacyclin). Circulating hormonal actions of AII include fl uid retention, direct vasoconstriction, and sympathetic neuromodulation, al l resulting in increased left ventricular preload and afterload. Because of these local sand hormonal characteristics, AII can immediately affect the myocardial balance of metabolic demand and supply rand long term can induce structural vascular and myocardial alterations. Pharmacologic inhibition o f AII production likely conveys myocardial and vascular protection in situa tions of acute myocardial oxygen debt. In the long term, inhibition of AII may attenuate structural changes in the coronary microcirculation related t o various cardiomyopathies or acute tissue injury, and direct antiatherogen ic effects may also occur.