Role of nitric oxide in regulation of coronary blood flow in response to increased metabolic demand in dogs with pacing-induced heart failure

The role of endothelium-derived nitric oxide (NO) in the metabolic control of coronary blood flow (CBF) in heart failure (HF) is poorly understood, so the present study investigated the effects of inhibitors of NO synthesis o n the response of CBF to changes in myocardial oxygen consumption (M(V) ove r dot O-2) in dogs with HF produced by rapid ventricular pacing and in cont rol dogs. The CBF, M(V) over dot O-2, and other hemodynamic parameters were measured in anesthetized animals. Before infusion of NIO-nitro-L-arginine methyl ester (L-NAME), the increases in CBF and M(V) over dot O-2 during pa cing tachycardia were not significantly different between the control and H F dogs. Intracoronary infusion of L-NAME did not alter the responses of CBF or M(V) over dot O-2 to pacing tachycardia in the control dogs, but in the HF dogs, it reduced the CBF response to pacing tachycardia without alterin g the tachycardia-induced changes in M(V) over dot O-2. Intracoronary infus ion of L-arginine reversed the effect of L-NAME. These results suggest that in HF dogs NO contributes to the regulation of CBF in response to an incre ased metabolic demand.