Effects of indomethacin on cerebral blood flow during hypercapnia in cats.
To study the contribution of prostaglandins to cerebral vasodilatation during hypercapnia, we inhibited prostaglandin synthesis with indomethacin. We measured cerebral blood flow (CBF) in anesthetized cats with 15-micrometers microspheres during normocapnia (PCO2 approximately 33 Torr), moderate hypercapnia (PCO2 approximately 49 Torr), and severe hypercapnia (PCO2 approximately 65 Torr) before and after intravenous 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. We examined efficacy and specificity of inhibition of prostaglandin synthesis by indomethacin using the cranial window method. Arachidonic acid (100 and 200 micrograms/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. Intravenous 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. This study suggests that steady-state cerebral vasodilatation during hypercapnia is largely preserved after inhibition of prostaglandin synthesis.
D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply; D002245:Carbon Dioxide / Q000097:blood; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006935:Hypercapnia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology*; D008863:Microspheres; D009928:Organ Specificity; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011448:Prostaglandin Antagonists / Q000494:pharmacology
D011448:Prostaglandin Antagonists; D002245:Carbon Dioxide; D010100:Oxygen; D007213:Indomethacin