Role of cyclooxygenase system in cerebrovascular responsiveness: different effects of indomethacin on CO2 responsiveness and dilatation by Ca(2+)-channel blocker.
To investigate roles of prostaglandins in the regulation of cerebral blood flow, we compared effects of indomethacin, a cyclooxygenase inhibitor, on the cerebrovascular CO2 responsiveness with those on the cerebrovascular dilatory action of diltiazem, a Ca(2+)-channel blocker. Fifteen adult cats were used. The cerebral tissue oxygen tension, carbon dioxide tension, pH and blood pressure were measured continuously. Indomethacin (1 mg/kg) was infused into the carotid artery. In 8 cats, 3 min inhalation of 5% CO2 in air was performed before and after the indomethacin infusion. In 7 cats, diltiazem (100 micrograms/kg) was infused into the carotid artery for 3 min before and after the indomethacin infusion. The cerebrovascular CO2 responsiveness was significantly decreased (p < 0.05) after the administration of indomethacin. On the other hand, the cerebrovascular dilatation induced by the Ca(2+)-channel blocker was significantly increased (p < 0.05) after the administration of indomethacin. It is concluded that the products of cyclooxygenase system are involved in the cerebrovascular responsiveness both to CO2 and to Ca(2+)-channel blocker, but action mechanisms of prostaglandins may be different, that is, prostaglandians may enhanced cerebrovascular responsiveness to CO2 but diminish it to Ca(2+)-channel blocker.
Izumi
Y
Y
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Gotoh
F
F
Fukuuchi
Y
Y
Isozumi
K
K
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism / Q000494:pharmacology; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004110:Diltiazem / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism
D011453:Prostaglandins; D002245:Carbon Dioxide; D011451:Prostaglandin-Endoperoxide Synthases; D004110:Diltiazem; D007213:Indomethacin