INHIBITION OF NITRIC-OXIDE SYNTHESIS DOES NOT AFFECT ISCHEMIC PRECONDITIONING IN ISOLATED-PERFUSED RAT HEARTS

Endothelium-derived nitric oxide (NO) has recently been reported to be a mediator of ischemic preconditioning in dog hearts. The aim of the present study was to determine the role of NO in ischemic precondition ing in isolated perfused rat hearts. Rat hearts were perfused at eithe r constant pressure (80 mmHg) or constant flow. After aerobic perfusio n (37 degrees C) for 10 min, hearts were treated with N-omega-nitro-L- arginine methyl ester (L-NAME; 30 mu M), which is an inhibitor of NO s ynthase, or vehicle. Ten minutes later, the hearts were preconditioned (4 episodes of 5 min of global ischemia and 5 min of reperfusion) or perfused normally before a 30-min global ischemic period. All hearts w ere reperfused for 30 min. Coronary flow or perfusion pressure plus he art rate and contractile function were measured continuously. Hearts p erfused at constant pressure and treated with 30 mu M L-NAME, a concen tration that effectively inhibits endogenous NO synthesis, exhibited d ecreased coronary flow after 10 min, and flow remained decreased throu ghout the experiment. Ischemic preconditioning before 30 min of global ischemia resulted in a doubling of contractile function and a reducti on of lactate dehydrogenase release at the end of the 30-min reperfusi on period compared with nonpreconditioned hearts. The protective effec t of preconditioning was not different in L-NAME-treated hearts. In ad dition, inhibition of NO synthase had no effect on the severity of isc hemia in nonpreconditioned hearts. Similar results were obtained in pr econditioned hearts that were perfused at constant flow, indicating th at the flow reductions caused by L-NAME did not influence the results. Under constant-flow conditions, L-NAME did increase the severity of i schemia in nonpreconditioned hearts. Despite the profound effects on c oronary flow, endogenous NO is not a mediator of ischemic precondition ing in isolated rat hearts.