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The vasodilatory response is known to be diminished in chronic heart failure. In the present study, we used dogs with chronic heart failure to investigate whether endothelium-dependent vasodilation in the resistance vessels in the hindlimb is decreased in chronic heart failure, and if so, to determine if endothelium-derived relaxing factor (EDRF) is involved in the mechanism. We induced heart failure in dogs by continuous rapid ventricular pacing. Under anesthesia, an internal carotid artery-femoral artery bypass system was established and perfusion pressure to the femoral artery was kept constant. Changes in hindlimb blood flow in response to various concentrations of acetylcholine (ACh), adenosine 5'-diphosphate disodium salt (ADP) and nitroglycerin (NTG) were examined in dogs with and without heart failure. The vasoconstrictive responses to L-NG-monomethyl L-arginine monoacetate (L-NMMA) were also studied. In dogs with heart failure, vasodilatory responses to both of the endothelium-dependent vasodilators, ACh and ADP, were decreased, while there were no differences in the responses to the endothelium-independent vasodilator NTG. The vasoconstrictive response to L-NMMA was diminished in heart failure. Thus, endothelium-dependent vasodilation in hindlimb resistance vessels is impaired in dogs with congestive heart failure. This impairment may be related to diminished EDRF/NO production or release in these vessels.

Impaired endothelium-dependent vasodilatory responses in hindlimb blood flow in dogs with congestive heart failure.