Nitric Oxide Plays a Beneficial Role in the Protective Action of Ramiprilat During Myocardial Ischemia / Reperfusion Injury
The goal of this investigation was to determine the possible role of nitric oxide in the action of the angiotensin controlling enzyme inhibitor, ramiprilat, to reduce myocardial ischemia/reperfusion injury. Ramiprilat, a nitric oxide synthase inhibitor (L-NAME), ramiprilat plus L-NAME, or a saline control (N=8 for each group), were administered in intact animal preparations of artificially induced acute myocardial ischemia. Anesthetized, open-chested rabbits were prepared for measurement of systemic hemodynamics. Animals were subjected to 30 min of left main coronary artery occlusion (marginal branch) followed by two hours of reperfusion. Ramiprilat (50 µg/kg, i.v.) or saline was administered 5 min prior to reperfusion, and those rabbits receiving L-NAME (100 µg/kg/min, i.v.) were pretreated starting before occlusion and continued throughout the remainder of the experiment. Myocardial infarct size (IS) was determined via tetrazolium staining and expressed as a percent of the myocardial area of risk (AR). lS/AR% was significantly lower in rabbits receiving ramiprilat (19±3% *) compared to those receiving saline (39±2%), ramiprilat plus L-NAME (43±4%) , or L-NAME alone (43±2%, Mean±SEM, *=p < 0.05). Neither AR as a percent of total left ventricular mass nor systemic hemodynamics were significantly different among any of the four treatment groups. The results indicate that the effect of ramiprilat to reduce infarct size is abolished by pretreatment with L-NAM E. Since earlier data suggest that ramiprilat protects myocardium by elevating bradykinin levels, this new result implies that the protection may be related to increased nitric oxide production mediated by bradykinin.