Depressed β-adrenergic receptor- and endothelium-mediated vasodilation in conscious dogs with heart failure

Abstract

Peripheral vasodilator responsiveness was examined in pacing-induced heart failure (HF) in 11 conscious dogs chronically instrumented for measurement of systemic (total peripheral resistance [TPR]) and local (iliac blood flow) vascular resistance. Dose responses to isoproterenol (ISO), acetylcholine (ACh), and nitroglycerin (NTG) were examined in the same dogs before pacing (control) and after 4 to 7 weeks of rapid ventricular pacing, which induced congestive HF, characterized by increased left ventricular end-diastolic pressure (6.7±0.4 [control] versus 28±1.5 [HF] mm Hg) and decreased cardiac output (-30±5%) and left ventricular dP/dt (-53±3%), as well as ascites and peripheral edema. In the control state, TPR fell by 57±2% in response to ISO (100 ng/kg), by 61±3% in response to ACh (3 μg/kg), and by 55±2% in response to NTG (10 μg/kg). In HF, smaller decreases (P