title: Effects of endothelin-1 on the cerebrovascular bed of the goat.
abstract: The aim of the present study was to analyze the effects of endothelin-1 (ET-1) in the cerebrovascular bed of the goat, the importance of endothelial integrity and the contribution of extracellular Ca2+ to these responses. We measured isometric tension and 45Ca2+ uptake in isolated middle cerebral arteries, and cerebral blood flow (CBF) in unanesthetized animals. ET-1 elicited concentration-dependent contractions which were potentiated in arteries without endothelium. Ca2(+)-free medium and nicardipine inhibited, and Bay K 8644 potentiated the ET-1-induced contractions. ET-1 enhanced 45Ca2+ uptake in isolated arteries. Injections of ET-1 directly into the cerebral circulation decreased CBF and increased cerebrovascular resistance in a dose-dependent manner. Infusion of nicardipine inhibited the ET-1-induced reductions in CBF. These results suggest that ET-1 reduces CBF of goats because of contraction of cerebral arteries by a direct action on smooth muscle, which is modulated by the endothelium and depends partially on the activation of Ca2+ influx through dihydropyridine-sensitive channels.
authors.affiliation: Centro de Investigación, Hospital La Fe, Universidad de Valencia, Spain.
authors.forename: J B
authors.initials: JB
authors.lastname: Salom
authors.forename: G
authors.initials: G
authors.lastname: Torregrosa
authors.forename: F J
authors.initials: FJ
authors.lastname: Miranda
authors.forename: J A
authors.initials: JA
authors.lastname: Alabadí
authors.forename: C
authors.initials: C
authors.lastname: Alvarez
authors.forename: E
authors.initials: E
authors.lastname: Alborch
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002132:Calcium Radioisotopes; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006041:Goats; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology
chemical_list: D002132:Calcium Radioisotopes; D016232:Endothelins; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009529:Nicardipine; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium