Role of the Cyclooxygenase System in Cerebrovascular Responsiveness: Different Effects of Indomethacin on CO₂ Responsiveness and Dilatation by Ca²⁺-channel Blocker

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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 Ca²⁺-channel blocker. Fifteen adult cats were used. The cerebral tissue oxygen tension, carbon dioxide tension, pH and blood pressure were measured continuously. Indomethacin (1mg/kg) was infused into the carotid artery. In 8 cats, 3min inhalation of 5% CO₂ in air was performed before and after the indomethacin infusion. In 7 cats, diltiazem (100μg/kg) was infused into the carotid artery for 3min 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 Ca²⁺-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 Ca²⁺-channel blocker, but action mechanisms of prostaglandins may be different, that is, prostaglandians may enhanced cerebrovascular responsiveness to CO₂ but diminish it to Ca²⁺-channel blocker.