Vasoconstrictive responses elicited by endothelin in bovine cerebral arteries.
1. Endothelin (ET-1) induced concentration-dependent contractions, which were slowly developed in segments of bovine cerebral arteries. Furthermore, this agent produced tachyphylaxis. 2. The contractions evoked by ET-1 were markedly reduced in Ca-free medium containing 1 mM EGTA and by the Ca channel antagonist, nifedipine (1 microM), but increased by the Ca channel agonist, BAY K 8644 (10 nM). 3. The contractions caused by ET-1 were significantly reduced by the protein kinase C (PKC) inhibitor, staurosporine (1 and 10 nM). 4. These results indicate that ET-1 induced potent vasoconstrictive responses, probably mediated by PKC activation, which were mainly dependent on extracellular Ca; this Ca enters the smooth muscle cells via dihydropyridine sensitive Ca channels.
Encabo
A
A
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Ferrer
M
M
Marín
J
J
Villamor
J
J
Balfagón
G
G
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects* / Q000201:enzymology; D016232:Endothelins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D009543:Nifedipine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D013618:Tachyphylaxis / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011493:Protein Kinase C; D009543:Nifedipine