The role of endogenous nitric oxide (NO) in modulating myocardial oxygen consumption (MV˙o 2) is unclear, in part because of systemic and coronary hemodynamic effects of blocking NO release. This study evaluated the effect of NO on right ventricular MV˙o 2 under controlled hemodynamic conditions. In 12 open-chest dogs, N ω-nitro-l-arginine methyl ester (l-NAME, 150 μg/min), a NO synthase (NOS) blocker, was infused into the right coronary artery. Heart rate and mean aortic pressure were constant. Right coronary blood flow and right ventricular MV˙o 2 were measured at normal and elevated right coronary perfusion pressures (RCP) before and afterl-NAME. To avoid effects of NO synthesis blockade on right coronary blood flow, which might have altered right ventricular MV˙o 2, experiments, were conducted during adenosine-induced maximal coronary vasodilation. l-NAME did not affect right coronary blood flow ( P = 0.51). However,l-NAME significantly increased right ventricular MV˙o 2 (6% at RCP 100 mmHg, and 21% at RCP 180 mmHg). Right coronary blood flow varied with perfusion pressure ( P < 0.02), and the elevation of MV˙o 2 produced by l-NAME increased at higher flows ( P < 0.04), consistent with the greater shear stress-mediated release of NO. These findings indicate that endogenous NO limits right ventricular MV˙o 2.
Role of nitric oxide and NADPH oxidase-derived superoxide in regulating coronary blood flow and metabolism in cardio-metabolic diseases
