Effects of endothelin-1 on the cerebrovascular bed of the goat.
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.
Salom
J B
JB
Centro de Investigación, Hospital La Fe, Universidad de Valencia, Spain.
Torregrosa
G
G
Miranda
F J
FJ
Alabadí
J A
JA
Alvarez
C
C
Alborch
E
E
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
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