BLOCKADE OF NITRIC-OXIDE SYNTHESIS REDUCES MYOCARDIAL OXYGEN-CONSUMPTION IN-VIVO

Background Although cardiac myocytes and coronary vascular endothelium are known to express a constitutive form of NO synthase, the in vivo effects of tonic endogenous production of NO on myocardial O-2 consump tion and contractile performance remain unclear. Methods and Results T he effects of blockade of NO synthase were determined in intact dogs. Myocardial O-2 consumption decreased systematically over a wide range of hemodynamic demand after the systemic administration of N-omega-nit ro-L-arginine methyl ester (L-NAME) or N-omega-nitro-L-arginine. Decre ases after doses of 1 and 10 mg/kg L-NAME averaged 23+/-3.8% and 34+/- 7.2% at a heart rate of 90 bpm in open-chest animals. Similar reductio ns occurred after the administration of L-NAME and N-omega-nitro-L-arg inine in chronically instrumented animals and were unaffected by beta- adrenergic blockade. Intracoronary infusion of L-NAME in chronically i nstrumented animals reduced both myocardial O-2 consumption and region al segment shortening, even at a dose that did not increase systemic a rterial pressure. Conclusions The blockade of NO synthesis reduces myo cardial O-2 consumption in vivo. The decrease in O-2 consumption is ac companied by a decrease in segment shortening. It involves a direct my ocardial action of NO, is unaffected by beta-blockade, and is consiste nt with in vitro studies indicating that low levels of NO augment cont ractile performance by inhibition of a cGMP-dependent phosphodiesteras e.