title: CO2 and cerebral circulation in newborn pigs: cyclic nucleotides and prostanoids in vascular regulation.
abstract: The role of cyclic nucleotides and prostanoids in cerebrovascular reactivity to increased carbon dioxide was investigated in anesthetized and artificially ventilated newborn pigs equipped with closed cranial windows. Pial arteriolar diameter was measured, and cortical periarachnoid cerebrospinal fluid (CSF) was collected from beneath the cranial window for determination of adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), and prostanoids. Progressively increasing arterial PCO2 (PaCO2) from normocapnia (33 +/- 1 mmHg) to hypercapnia (final PaCO2, 83 +/- 2 mmHg) resulted in dose-dependent pial arteriolar dilation and concomitant increases in cAMP, cGMP, and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) in cortical CSF. N omega-methyl-L-arginine, N omega-nitro-L-arginine, N omega-nitro-L-arginine methyl ester, methylene blue, and LY 83583 did not inhibit cerebral vasodilation or the increases in cortical cAMP/cGMP induced by hypercapnia. Indomethacin abolished the vasodilatory response to hypercapnia and attenuated the hypercapnia-induced increases in cAMP and cGMP. Prostacyclin analogues increased both cAMP and cGMP levels in cortical CSF and induced pial arteriolar dilation (iloprost > carbaprostacyclin). The present data suggest that in newborn pigs cyclic nucleotides are involved in cerebral vasodilation in response to hypercapnia via a prostanoid-dependent mechanism.
authors.affiliation: Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.
authors.forename: H
authors.initials: H
authors.lastname: Parfenova
authors.forename: M
authors.initials: M
authors.lastname: Shibata
authors.forename: S
authors.initials: S
authors.lastname: Zuckerman
authors.forename: C W
authors.initials: CW
authors.lastname: Leffler
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000502:physiology; D001808:Blood Vessels / Q000502:physiology; D002245:Carbon Dioxide / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology; D006935:Hypercapnia / Q000378:metabolism / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D019001:Nitric Oxide Synthase; D009712:Nucleotides, Cyclic / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000502:physiology*; D010841:Pia Mater / Q000098:blood supply; D011453:Prostaglandins / Q000378:metabolism / Q000502:physiology*; D014664:Vasodilation
chemical_list: D009712:Nucleotides, Cyclic; D011453:Prostaglandins; D002245:Carbon Dioxide; D011464:Epoprostenol; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007213:Indomethacin