Endothelin-1-induced vascular contractions: interactions with drugs affecting the calcium channel.
Recently, a potent vasoconstrictor peptide, endothelin-1 (ET-1), was isolated from vascular endothelial cells. We investigated the inhibition of ET-1-induced contractions on isolated porcine coronary artery and rabbit aorta by calcium antagonists of the 1,4-dihydropyridine type. In addition, the vasoconstriction induced by ET-1 was compared with that induced by the calcium agonist (-)Bay K 8644. The calcium antagonists nitrendipine and nicardipine partially antagonize the vasoconstrictive effects of ET-1 in a dose-dependent manner, but this antagonism is only functional and noncompetitive. In the isolated rabbit aortic ring, ET-1 induces a half-maximal contraction. In contrast, the calcium agonist (-)Bay K 8644 has no effect on this preparation. However, when the vessels are partly depolarized by adding 15 mM K+, (-)Bay K 8644 and ET-1 express their full activity. Again here, the concentration-response curve of ET-1 is depressed by increasing concentrations of nitrendipine, but only functionally, noncompetitively. These results suggest that ET-1 acts through specific receptors different from the 1,4-dihydropyridine selective site.
Stasch
J P
JP
Institute of Pharmacology, Bayer AG, Wuppertal, F.R.G.
Kazda
S
S
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D016232:Endothelins; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009568:Nitrendipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D013552:Swine
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D016232:Endothelins; D010455:Peptides; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine