HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (18) Citing Articles via Google Scholar Google Scholar Articles by Carratu, P. Articles by Parfenova, H. Search for Related Content PubMed PubMed Citation Articles by Carratu, P. Articles by Parfenova, H.

Endogenous heme oxygenase prevents impairment of cerebral vascular functions caused by seizures

Laboratory for Research in Neonatal Physiology, Departments of Physiology and Pediatrics, and Vascular Biology Center, University of Tennessee Health Science Center, Memphis, Tennessee 38163

Submitted 28 January 2003 ; accepted in final form 8 May 2003

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.

cerebral circulation; seizure; bicuculline; carbon monoxide; tin protoporphyrin; vascular injury; vascular reactivity; pial arterioles; cranial window; newborn piglets

This article has been cited by other articles:

				X. Qin, H. Kwansa, E. Bucci, S. Dore, D. Boehning, D. Shugar, and R. C. Koehler Role of heme oxygenase-2 in pial arteriolar response to acetylcholine in mice with and without transfusion of cell-free hemoglobin polymers Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R498 - R504. [Abstract] [Full Text] [PDF]

				A. Kanu and C. W. Leffler Carbon monoxide and Ca2+-activated K+ channels in cerebral arteriolar responses to glutamate and hypoxia in newborn pigs Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3193 - H3200. [Abstract] [Full Text] [PDF]

				A. Zimmermann, C. W. Leffler, D. Tcheranova, A. L. Fedinec, and H. Parfenova Cerebroprotective effects of the CO-releasing molecule CORM-A1 against seizure-induced neonatal vascular injury Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2501 - H2507. [Abstract] [Full Text] [PDF]

				C. W. Leffler, H. Parfenova, A. L. Fedinec, S. Basuroy, and D. Tcheranova Contributions of astrocytes and CO to pial arteriolar dilation to glutamate in newborn pigs Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2897 - H2904. [Abstract] [Full Text] [PDF]

				S. Basuroy, S. Bhattacharya, D. Tcheranova, Y. Qu, R. F. Regan, C. W. Leffler, and H. Parfenova HO-2 provides endogenous protection against oxidative stress and apoptosis caused by TNF-{alpha} in cerebral vascular endothelial cells Am J Physiol Cell Physiol, November 1, 2006; 291(5): C897 - C908. [Abstract] [Full Text] [PDF]

				A. Kanu, J. Whitfield, and C. W. Leffler Carbon monoxide contributes to hypotension-induced cerebrovascular vasodilation in piglets Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2409 - H2414. [Abstract] [Full Text] [PDF]

				H. Parfenova, S. Basuroy, S. Bhattacharya, D. Tcheranova, Y. Qu, R. F. Regan, and C. W. Leffler Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection Am J Physiol Cell Physiol, May 1, 2006; 290(5): C1399 - C1410. [Abstract] [Full Text] [PDF]

				C. W. Leffler, H. Parfenova, J. H. Jaggar, and R. Wang Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation J Appl Physiol, March 1, 2006; 100(3): 1065 - 1076. [Abstract] [Full Text] [PDF]

				H. Parfenova, P. Carratu, D. Tcheranova, A. Fedinec, M. Pourcyrous, and C. W. Leffler Epileptic seizures cause extended postictal cerebral vascular dysfunction that is prevented by HO-1 overexpression Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2843 - H2850. [Abstract] [Full Text] [PDF]

				A. Ahmed, C. M. Waters, C. W. Leffler, and J. H. Jaggar Ionic mechanisms mediating the myogenic response in newborn porcine cerebral arteries Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2061 - H2069. [Abstract] [Full Text] [PDF]

				E. Barkoudah, J. H. Jaggar, and C. W. Leffler The permissive role of endothelial NO in CO-induced cerebrovascular dilation Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1459 - H1465. [Abstract] [Full Text] [PDF]

				Q. Xi, D. Tcheranova, H. Parfenova, B. Horowitz, C. W. Leffler, and J. H. Jaggar Carbon monoxide activates KCa channels in newborn arteriole smooth muscle cells by increasing apparent Ca2+ sensitivity of {alpha}-subunits Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H610 - H618. [Abstract] [Full Text] [PDF]