A pharmacological study on the mechanism of the endothelin-induced contraction of the bovine cerebral artery]

Using helical strips of the bovine middle cerebral arteries, changes in vascular tension were measured during isometric contractions induced by endothelin. 1) Both Ca(++)-free media and Ca(++)-antagonists depressed the endothelin-induced contractions only by 40% of the control, suggesting the involvement of both Ca(++)-entry from outside the muscle cell and intracellular Ca(++)-release from the sarcoplasmic reticulum. 2) Endothelin-induced contractions were significantly depressed by 1 microgram/ml tetrodotoxin (TTX). Relative size of depression by TTX was practically the same as that observed in Na(+)-free media without TTX. These results indicated a partial involvement of Na(+)-entry through TTX-sensitive Na(+)-channels. 3) Endothelin-induced contractions were effectively depressed by NCDC, an inhibitor of phospholipase C, suggesting the involvement of PI-turnover in the contraction. 4) Protein kinase inhibitors such as H-7 and H-8 effectively depressed endothelin-induced contractions. This result suggested the phosphorylation of a certain protein by protein kinase C as a cause of long lasting contractions. 5) A phospholipase A2 (PL A2) inhibitor, quinacrine, significantly depressed the endothelin-induced contractions, suggesting a possible involvement of PL A2. However, neither the cyclooxygenase inhibitor nor the lipoxygenase inhibitor depressed endothelin-induced contractions.