title: Influence of hypoxia/ischemia on cerebrovascular responses to oxytocin in piglets.
abstract: We examined the effects of hypoxic/ischemic stress on cerebral arteriolar responses to oxytocin in anesthetized piglets. Pial arteriolar diameters were measured using a cranial window and intravital microscopy. First, we evaluated arteriolar responses to topical application of oxytocin during normoxic conditions. We then determined whether 5-10 min of arterial hypoxia, ischemia, or asphyxia alters oxytocin-induced responses. Arterial hypoxia was produced by inhalation of 7.5% O2-92.5% N2 for 10 min. Ischemia was achieved by increasing intracranial pressure for 10 min. Asphyxia was achieved by turning off the ventilator for 5 min. During normoxic conditions, oxytocin dilated pial arterioles by 9 +/- 1% at 10(-8) and by 16 +/- 1% at 10(-6) mol/l (n = 47, p < 0.05). Arteriolar responses to oxytocin did not change with repeated applications (n = 10). Following hypoxia, dilator effect of oxytocin was not changed at 10(-8) (8 +/- 2%) but it was reduced at 10(-6) mol/l (7 +/- 2%; p < 0.05, n = 8). After asphyxia or ischemia, oxytocin did not dilate arterioles at 10(-8) mol/l, whereas 10(-6) mol/l resulted in a mild vasoconstriction (-4 +/- 3 to -6 +/- 4%, n = 6 and 8). Topically applied superoxide dismutase did not preserve arteriolar responses to oxytocin after asphyxia although the arterioles did not constrict to 10(-6) mol/l oxytocin (n = 5). Dilatation of cerebral arterioles in response to oxytocin was reversed to constriction by N(omega)-nitro-L-arginine methyl ester (L-NAME) (15 mg/kg, i.v.; n = 5) and by endothelial impairment by intra-arterial infusion of phorbol ester (10[-5] mol/l; n = 5). We conclude that the absence of pial arteriolar dilation to oxytocin after ischemia and asphyxia indicates endothelial dysfunction which may be involved in the pathology of perinatal brain injury.
authors.affiliation: Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, N.C. 27157-1083, USA. fbari@bgsm.edu
authors.forename: F
authors.initials: F
authors.lastname: Bari
authors.forename: R A
authors.initials: RA
authors.lastname: Errico
authors.forename: T M
authors.initials: TM
authors.lastname: Louis
authors.forename: D W
authors.initials: DW
authors.lastname: Busija
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000098:blood supply*; D002545:Brain Ischemia / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010121:Oxytocin / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation
chemical_list: D015221:Potassium Channels; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D013481:Superoxides; D009569:Nitric Oxide; D010121:Oxytocin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid