Mechanical performance and coronary flow adjustments to changes in workload are not affected by inhibiting nitric...

The importance of NO-induced vasodilator tone in maintaining adequate coronary flow to sustain hemodynamic function in aerobic heart and the role of endothelial release of NO in reactive hyperemia was studied in isolated working and Langendorff perfused rat heart, respectively. Raising the preload from 0 to 20 cm H2O caused a linear increase in coronary flow, myocardial oxygen consumption (MVO2) and cardiac output in the untreated working hearts and in the hearts in which basal release of NO has been inhibited by NG-monomethyl L-arginine (L-NMMA, 200 microM). L-NMMA, but not L-arginine, reduced coronary flow by 48% and 21.5% at preload levels of 0 and 20 cm H2O, respectively. A steeper coronary flow/preload relation and an increased O2 extraction in L-NMMA treated hearts allowed for the fact that their MVO2, lactate release and cardiac output were not significantly different from those in the untreated hearts at any of the preload level tested. SIN-1, 10 microM, augmented coronary flow to 136% and 107% at preload levels of 0 and 20 cm H2O, respectively, indicating that coronary vascular reserve was preserved at all preloads tested. L-NMMA-treatment greatly reduced reactive hyperemia following 30 s occlusion period and it significantly increased hyperemia following 10 min occlusion period. These findings provide evidence that while the inhibition of NO synthesis reduces coronary flow it does not induce a state of ischemia in isolated rat heart.