title: Coronary beta-adrenoceptor function is modified by the endothelium in heart failure.
abstract: Congestive heart failure is associated with abnormalities in myocardial beta-adrenoceptor function. The extent of vascular beta-adrenoceptor alterations at heart failure, however, is unknown. Accordingly, we examined beta-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 x min-1, respectively). At early heart failure, (1) CRX with endothelium were more sensitive to isoproterenol than CRX without endothelium (EC50: 1.1 x 10(-8) vs. 1.6 x 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-EC50: end-stage heart failure: 1.1 x 10(-7) vs. control: 1.8 x 10(-8)M,p<0.05; and LAD-EC50: end-stage heart failure: 8.8 x 10(-7) M vs. control: 8.3 x 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 beta-adrenoceptor stimulation is coronary artery-dependent, and modulated not only by the heart failure state, but also by the presence of a functional endothelium.
authors.affiliation: Department of Pharmacology, University of Toronto, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Larosa
authors.forename: C
authors.initials: C
authors.lastname: Forster
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000503:physiopathology*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D015237:Dinoprost; D007545:Isoproterenol