title: Inhibitory role of the coronary arterial endothelium to alpha-adrenergic stimulation in experimental heart failure.
abstract: The role of the endothelium in regulating coronary alpha-adrenergic tone was evaluated in isolated coronary arterial rings from dogs with and without pacing-induced congestive heart failure (CHF). The maximal contractile response to methoxamine was attenuated approximately 43% (p less than 0.05) in both intact and denuded CHF rings compared with control. Conversely, norepinephrine-induced contractions were diminished 58% in intact CHF vessels and 39% in denuded CHF vessels (p less than 0.05). Denudation did not alter responses to methoxamine but significantly (p less than 0.05) augmented the tension generated by norepinephrine in both control (1.7-fold) and CHF (2.4-fold) arteries. In both intact control and CHF coronary arteries, norepinephrine elicited rapid, transient relaxations that preceded slow, sustained contractions; the initial relaxation phase was endothelium dependent, because denudation eliminated the response. Relaxations to the selective alpha 2-adrenoceptor agonist BHT 920 were also dependent on the presence of an endothelium. At peak CHF, endothelium-dependent relaxations to norepinephrine and BHT 920 were enhanced, whereas relaxations to nitroglycerin and acetylcholine were unaltered. The data suggest that alpha-adrenergic tone in canine coronary arteries is diminished by pacing-induced CHF because of a decrease in alpha 1-adrenoceptor-mediated constriction and an enhanced capacity of the endothelium to antagonize the direct vascular smooth muscle response of norepinephrine through endothelium-dependent, alpha 2-adrenoceptor-mediated relaxations.
authors.affiliation: Department of Medicine, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Main
authors.forename: C
authors.initials: C
authors.lastname: Forster
authors.forename: P W
authors.initials: PW
authors.lastname: Armstrong
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D006706:Homeostasis; D066298:In Vitro Techniques; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology
chemical_list: D011942:Receptors, Adrenergic, alpha; D011189:Potassium Chloride; D015237:Dinoprost; D008729:Methoxamine; D000109:Acetylcholine; D009638:Norepinephrine