Pharmacology of endothelin-1 in isolated vessels: effect of nicardipine, methylene blue, hemoglobin, and gossypol.
Sensitive bioassay tissues for porcine endothelin-1 (ET-1) were developed in a cascade superfusion system and in organ baths. Venous preparations of the rabbit and rat were more sensitive than arterial preparations. ET-1 had a different pharmacological profile than Bay K 8644 on the various preparations. Nicardipine (0.1-1 microM) abolished the responses to Bay K 8644 without affecting those induced by ET-1. Thus, ET-1 contracts venous and some arterial vessels via specific receptors or channels that differ from dihydropyridine-sensitive calcium channels. Methylene blue and hemoglobin potentiated responses to ET-1 in endothelium-denuded venous vessels, whereas gossypol had no effect.
D'Orleans-Juste
P
P
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, England.
Finet
M
M
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; D001158:Arteries / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D016232:Endothelins; D006072:Gossypol / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; 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 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014680:Veins / Q000187:drug effects
D015220:Calcium Channels; D016232:Endothelins; D006454:Hemoglobins; D010455:Peptides; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009529:Nicardipine; D006072:Gossypol; D008751:Methylene Blue; D007213:Indomethacin