Effects of indomethacin on cerebral blood flow during hypercapnia in cats

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Abstract
To study the contribution of prostaglandins to cerebral vasodilatation during hypercapnia, prostaglandin synthesis was inhibited with indomethacin. Cerebral blood flow (CBF) in anesthetized cats was measured with 15-.mu.m microspheres during normocapnia (PCO2 [partial pressure of CO2] .apprx. 33 Torr), moderate hypercapnia (PCO2 .apprx. 49 Torr), and severe hypercapnia (PCO2 .apprx. 65 Torr) before and after i.v. administration of vehicle or indomethacin (3 and 10 mg/kg). Hypercapnia produced graded increments in blood flow to all areas of the brain. Administration of indomethacin did not change control CBF or significantly attenuate increases in CBF during hypercapnia. Efficacy and specificity of inhibition of prostaglandin synthesis was examined by indomethacin using the cranial window method. Arachidonic acid (100 and 200 .mu.g/ml) and acetylcholine (10-7 and 10-6 M or 10-6 and 10-5 M), dissolved in artificial cerebrospinal fluid, dilated pial arteries in a dose-dependent fashion. I.v. administration of indomethacin blocked vasodilatation produced by arachidonic acid but did not affect the response to acetylcholine. Thus, indomethacin, at a dose that effectively blocks prostaglandin synthesis, did not alter resting CBF or attenuate the increase in CBF during hypercapnia. Apparently, steady-state cerebral vasodilatation during hypercapnia is largely preserved after inhibition of prostaglandin synthesis.