Endothelium-dependent relaxations in canine coronary arteries are enhanced in early heart failure and persist in recovery.
In vitro coronary artery responsiveness to noradrenaline, phenylephrine, and BHT-920 together with functional relaxation to acetylcholine was assessed in dogs at the early onset of pacing-induced heart failure (1 week) and in dogs recovered from heart failure (3 weeks paced, followed by 4 weeks discontinued pacing). alpha-Adrenoceptor stimulation produced contractile responses that were unaltered in early congestive heart failure and recovery. Contractions to noradrenaline and BHT-920 were always less than those produced by phenylephrine. Endothelium-intact arteries demonstrated relaxations in response to noradrenaline and BHT-920, but not phenylephrine. Relaxations to noradrenaline were enhanced 24% in early heart failure and 47% following recovery from heart failure, compared with control. BHT-920 produced relaxations that were augmented 21 and 76% in early heart failure and recovery, respectively. Contractile sensitivity to noradrenaline increased 5-fold in early heart failure and was not different in recovery, compared with control. Contractile sensitivity to BHT-920 and phenylephrine was unaltered throughout. Acetylcholine produced relaxations that were increased 21% in early heart failure and 13% after recovery from congestive heart failure. Furthermore, acetylcholine sensitivity was significantly enhanced in early heart failure and recovery. The current study reveals a progressive adaptation of the coronary endothelium in congestive heart failure, possibly directed towards protection against excessive vasoconstriction due to circulating catecholamines.
Larosa
G
G
Department of Medicine, St. Michael's Hospital, Toronto, ON, Canada.
Armstrong
P W
PW
Forster
C
C
D000109:Acetylcholine / Q000494:pharmacology; D000222:Adaptation, Physiological; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006333:Heart Failure / Q000503:physiopathology*; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D010656:Phenylephrine; C024763:talipexole; D000109:Acetylcholine; D009638:Norepinephrine