Endothelin-1 contracts isolated vessels independently of dihydropyridine-sensitive Ca2+ channel activation.
Spirally cut strips of arteries and veins were prepared from the rabbit or the dog and superfused in cascade. Venous strips were more sensitive to endothelin-1 (ET-1) than arterial ones and, in particular, the rabbit jugular and the rabbit mesenteric veins were contracted by as little as 0.5-2.5 pmol of ET-1 in a reproducible and dose-dependent way. The calcium agonist Bay K 8644 had a different profile of activity on the vascular strips, being more potent on the rabbit mesenteric artery than on the rabbit jugular or mesenteric veins. Nicardipine (10(-7) M) did not affect the ET-1-induced vascular contractions but abolished the contractile activity of Bay K 8644. Contractions induced by ET-1 were not affected by the kininase II inhibitor captopril in the rabbit jugular veins but were potentiated by methylene blue in both veins of the rabbit. Our results indicate that ET-1 potently contracts venous and arterial isolated vessels via the activation of specific receptors or channels that differ from the dihydropyridine-sensitive calcium channels. The fact that ET-1 is more active on venous than on arterial smooth muscle may have important pathophysiological implications.
D'Orleans-Juste
P
P
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, U.K.
De Nucci
G
G
Vane
J R
JR
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D016232:Endothelins; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D004095:Dihydropyridines; D016232:Endothelins; D010455:Peptides; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002216:Captopril; D009529:Nicardipine; D008751:Methylene Blue