Blockade of Nitric Oxide Synthesis Reduces Myocardial Oxygen Consumption In Vivo

Abstract

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 consumption and contractile performance remain unclear. Methods and Results The 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 ^ω -nitro- l -arginine methyl ester (L-NAME) or N ^ω -nitro- l -arginine. Decreases 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 reductions occurred after the administration of L-NAME and N ^ω -nitro- l -arginine in chronically instrumented animals and were unaffected by β-adrenergic blockade. Intracoronary infusion of L-NAME in chronically instrumented animals reduced both myocardial O ₂ consumption and regional segment shortening, even at a dose that did not increase systemic arterial pressure. Conclusions The blockade of NO synthesis reduces myocardial O ₂ consumption in vivo. The decrease in O ₂ consumption is accompanied by a decrease in segment shortening. It involves a direct myocardial action of NO, is unaffected by β-blockade, and is consistent with in vitro studies indicating that low levels of NO augment contractile performance by inhibition of a cGMP-dependent phosphodiesterase.