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 on the response of CBF to changes in myocardial oxygen consumption (M(V) over dot O-2) in dogs with HF produced by rapid ventricular pacing and in control 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 pacing tachycardia were not significantly different between the control and HF 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 altering the tachycardia-induced changes in M(V) over dot O-2. Intracoronary infusion 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 increased metabolic demand.