Coronary β-Adrenoceptor Function Is Modified by the Endothelium in Heart Failure

Abstract

Congestive heart failure is associated with abnormalities in myocardial β-adrenoceptor function. The extent of vascular β-adrenoceptor alterations at heart failure, however, is unknown. Accordingly, we examined β-adrenoceptor-mediated relaxations in both circumflex (CRX) and left anterior descending (LAD) coronary arteries with and without endothelium from dogs in early and end-stage heart failure induced by rapid ventricular pacing (1 and 4 weeks pacing at 250 beats·mkr¹, respectively). At early heart failure, (1) CRX with endothelium were more sensitive to isoproterenol than CRX without endothelium (EC₅₀: 1.1 × 10^–8 vs. 1.6 × 10^–7 M, p < 0.05); and (2) in response to salbutamol, CRX with endothelium had a lower maximum relaxation response than CRX without endothelium (56.6 vs. 75.9%, p < 0.05). At end-stage heart failure, (1) endothelium-intact CRX and LAD showed a significant decrease in sensitivity to isoproterenol compared to control (CRX- EC_50: end-stage heart failure: 1.1 × 10^–7 vs. control: 1.8 × 10^–8 M, p < 0.05; and LAD-EC₅₀: end-stage heart failure: 8.8 × 10^–7 M vs. control: 8.3 × 10^-8 M, p < 0.05); (2) LAD with endothelium showed greater maximum relaxation to salbutamol than LAD without endothelium (100.8 vs. 76.5%, p < 0.05); and (3) CRX were significantly more sensitive to isoproterenol than LAD. These data suggest that coronary vascular tone via β-adrenoceptor stimulation is coronary artery-dependent, and modulated not only by the heart failure state, but also by the presence of a functional endothelium.