title: Endogenous heme oxygenase prevents impairment of cerebral vascular functions caused by seizures.
abstract: In newborn pigs, the mechanism of seizure-induced cerebral hyperemia involves carbon monoxide (CO), the vasodilator product of heme catabolism by heme oxygenase (HO). We hypothesized that seizures cause cerebral vascular dysfunction when HO activity is inhibited. With the use of cranial window techniques, we examined cerebral vascular responses to endothelium-dependent (hypercapnia and bradykinin) and endothelium-independent (isoproterenol and sodium nitroprusside) dilators during the recovery from bicuculline-induced seizures in saline controls and in animals pretreated with a HO inhibitor, tin protoporphyrin (SnPP). SnPP (3 mg/kg iv) blocked dilation to heme and reduced the CO level in cortical periarachnoid cerebrospinal fluid, indicating HO inhibition in the cerebral microcirculation. In saline control piglets, seizures increased the CO level, which correlated with the time-dependent cerebral vasodilation; during the recovery (2 h after seizure induction), responses to all vasodilators were preserved. In SnPP-treated animals, cerebral vasodilation and the CO responses to seizures were greatly reduced, and cerebral vascular reactivity was severely impaired during the recovery. These findings suggest that HO in the cerebral microcirculation is rapidly activated during seizures and provides endogenous protection against seizure-induced vascular injury.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, 894 Union Avenue, Memphis, TN 38163, USA.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Carratu
authors.forename: Massroor
authors.initials: M
authors.lastname: Pourcyrous
authors.forename: Alex
authors.initials: A
authors.lastname: Fedinec
authors.forename: Charles W
authors.initials: CW
authors.lastname: Leffler
authors.forename: Helena
authors.initials: H
authors.lastname: Parfenova
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001099:Arachnoid / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology; D002196:Capillaries / Q000201:enzymology; D002248:Carbon Monoxide / Q000097:blood / Q000134:cerebrospinal fluid; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000378:metabolism* / Q000503:physiopathology*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006935:Hypercapnia / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D008665:Metalloporphyrins / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D013552:Swine
chemical_list: D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D020030:Nitric Oxide Donors; D011524:Protoporphyrins; D009599:Nitroprusside; D002248:Carbon Monoxide; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D007545:Isoproterenol; D001920:Bradykinin