INDOMETHACIN ABOLISHES CEREBRAL BLOOD-FLOW INCREASE IN RESPONSE TO ACETAZOLAMIDE-INDUCED EXTRACELLULAR ACIDOSIS - A MECHANISM FOR ITS EFFECT ON HYPERCAPNIA

Indomethacin is known to attenuate quite markedly the increase in CBF during hypercapnia. Hypercapnia is, in all likelihood, mediated by the acid shift at the level of the smooth muscle cells of the cerebral ar terioles. We therefore investigated the effect of indomethacin on the CBF increase caused by acetazolamide (Az), a drug that induces brain e xtracellular acidosis, which triggers its effect on CBF. We compared t he results to the inhibitory effect of indomethacin on the CBF increas e during hypercapnia. Indomethacin but not diclofenac, another potent cyclooxygenase inhibitor, was found to block almost completely the CBF increase caused by Az-induced extracellular acidosis or by CO2, but i t did not influence the CBF increase produced by sodium nitroprusside or papaverine. The results suggest that indomethacin exerts its action on CO, reactivity by a nonprostaglandin-mediated mechanism that direc tly interferes with the regulation of cerebrovascular tone mediated by extracellular pH.