Effects of endothelin-1 on the cerebrovascular bed of the goat

Eur J Pharmacol. 1991 Jan 3;192(1):39-45. doi: 10.1016/0014-2999(91)90066-y.

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.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Acetylcholine / pharmacology
  • Animals
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Radioisotopes
  • Cerebrovascular Circulation / drug effects*
  • Endothelins / pharmacology*
  • Female
  • Goats
  • In Vitro Techniques
  • Isometric Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Nicardipine / pharmacology
  • Potassium / pharmacology

Substances

  • Calcium Radioisotopes
  • Endothelins
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Nicardipine
  • Acetylcholine
  • Potassium
  • Calcium