[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.
Kojo
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1st Department of Physiology, Iwate Medical University, School of Medicine, Japan.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects*; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D001095:Arachidonic Acids; D016232:Endothelins; D007546:Isoquinolines; D010879:Piperazines; D015222:Sodium Channels; D016718:Arachidonic Acid; D013779:Tetrodotoxin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D011796:Quinacrine; D002118:Calcium