title: Indomethacin-sensitive CO2 reactivity of cerebral arterioles is restored by vasodilator prostaglandin.
abstract: To investigate the role of vasodilator prostanoids in the CO2-induced relaxation of cerebral arterioles, the present study examined the effect of exogenous prostaglandin (PG) E2 and nonprostanoid vasodilators, adenosine and sodium nitroprusside, on the indomethacin-impaired pial arteriolar response to CO2 in newborn piglets. Reactivity of pial arterioles (52-131 microns diam) was determined using a closed cranial window with intravital microscopy. Cortical prostanoid synthesis was assessed by analyzing for select prostanoids in cerebrospinal fluid sampled from under the cranial window. Inhalation of 7% CO2 caused an elevation of cortical 6-keto-PGF1 alpha and thromboxane (Tx) B2 and increased pial arteriolar diameter by 34 +/- 5%. Two cyclooxygenase inhibitors, indomethacin (5 mg/kg i.v.) and ibuprofen (30 mg/kg i.v.), abolished the CO2-induced elevation of cortical prostanoids. Indomethacin, but not ibuprofen, blocked the CO2-induced increase in pial arteriolar diameter. The indomethacin-impaired vasodilator response to CO2 was restored when PGE2 (0.1-1 microM) was applied topically to the cortical surface. Adenosine (1-100 microM) and sodium nitroprusside (0.5 microM) only partially restored the vasodilator response to CO2. The data suggest that vasodilator prostanoids facilitate cerebrovascular relaxation to CO2 and may play a permissive role in the relaxation response of vascular smooth muscle. The fact that adenosine (adenosine 3',5'-cyclic monophosphate-mediated dilator) and sodium nitroprusside (guanosine 3',5'-cyclic monophosphate-mediated dilator), were partially effective suggests a role for those intracellular signaling pathways. We speculate that receptor activation of intracellular pathways may alter Ca2+ sensitivity of the contractile apparatus in such a way that the relaxation response to CO2 can occur.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors.forename: L C
authors.initials: LC
authors.lastname: Wagerle
authors.forename: P A
authors.initials: PA
authors.lastname: Degiulio
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects; D002245:Carbon Dioxide / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply; D011453:Prostaglandins / Q000096:biosynthesis / Q000494:pharmacology*; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D011453:Prostaglandins; D014665:Vasodilator Agents; D002245:Carbon Dioxide; D007052:Ibuprofen; D007213:Indomethacin