Role of endothelin in alpha-adrenoceptor coronary vasoconstriction.
It has been proposed that alpha-adrenoceptor vasoconstriction in coronary resistance vessels results not from alpha-adrenoceptors on coronary smooth muscle but from alpha-adrenoceptors on cardiac myocytes that stimulate endothelin (ET) release. The present experiments tested the hypothesis that the alpha-adrenoceptor-mediated coronary vasoconstriction that normally occurs during exercise is due to endothelin. In conscious dogs (n = 10), the endothelin ET(A)/ET(B) receptor antagonist tezosentan (1 mg/kg iv) increased coronary venous oxygen tension at rest but not during treadmill exercise. This result indicates that basal endothelin levels produce a coronary vasoconstriction at rest that is not observed during the coronary vasodilation during exercise. In contrast, the alpha-adrenoceptor antagonist phentolamine increased coronary venous oxygen tension during exercise but not at rest. The difference between the endothelin blockade and alpha-adrenoceptor blockade results indicates that alpha-adrenoceptor coronary vasoconstriction during exercise is not due to endothelin. However, in anesthetized dogs, bolus intracoronary injections of the alpha-adrenoceptor agonist phenylephrine produced reductions in coronary blood flow that were partially antagonized by endothelin receptor blockade with tezosentan. These results are best explained if alpha-adrenoceptor-induced endothelin release requires high pharmacological concentrations of catecholamines that are not reached during exercise.
Gorman
Mark W
MW
Dept. of Physiology and Biophysics, Box 357290, University of Washington School of Medicine, Seattle, WA 98195-7290, USA. mgorman@u.washington.edu
Farias
Martin
M
Richmond
Keith N
KN
Tune
Johnathan D
JD
Feigl
Eric O
EO
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D016232:Endothelins / Q000502:physiology*; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D005082:Physical Exertion / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D016232:Endothelins; D011725:Pyridines; D011942:Receptors, Adrenergic, alpha; D013777:Tetrazoles; D014665:Vasodilator Agents; D010656:Phenylephrine; C120582:tezosentan