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) All Versions of this Article: 288/2/H962    most recent 01218.2003v1 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 (6) Citing Articles via Google Scholar Google Scholar Articles by Govindaraju, V. Articles by Ward, M. E. Search for Related Content PubMed PubMed Citation Articles by Govindaraju, V. Articles by Ward, M. E.

Interaction between endothelial heme oxygenase-2 and endothelin-1 in altered aortic reactivity after hypoxia in rats

²Division of Respirology and Department of Critical Care, St Michael's Hospital, University of Toronto, Toronto, Ontario; and ¹Meakins Christie Laboratories and ³Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada

Submitted 22 December 2003 ; accepted in final form 5 October 2004

The aim of this study was to determine whether increased expression of heme oxygenase (HO) contributes to impairment of aortic contractile responses after hypoxia through effects on reactivity to endothelin-1 (ET-1). Thoracic aortas from normoxic rats and rats exposed to hypoxia (10% O₂) for 16 or 48 h were mounted in organ bath myographs for contractile studies, fixed in paraformaldehyde, or frozen in liquid nitrogen for protein extraction. In rings from normoxic rats, the HO inhibitor tin protoporphyrin IX (SnPP IX, 10 µM) did not alter the response to phenylephrine or ET-1. In rings from rats exposed to 16-h hypoxia, maximum tension generated in response to these agonists was higher in endothelium-intact but not -denuded rings in the presence of SnPP IX. In rings from rats exposed to 48-h hypoxia SnPP IX increased contraction in endothelium-intact but not -denuded rings. In endothelium-intact aortic rings from rats exposed to 16-h hypoxia incubated with endothelin A receptor-specific antagonist BQ-123 (10^–7 M), SnPP IX did not alter phenylephrine-induced contraction. Aortic ET-1 protein levels, measured by radioimmunoassay, were increased in rats exposed to hypoxia for 16 and 48 h. Western blotting showed that HO-1 and HO-2 protein were increased after 16 h of hypoxia and returned to near-control levels after 48 h. Increase in HO-1 protein was detected in endothelium-intact and -denuded rings. Removal of endothelium abolished the increase in HO-2 immunoreactivity. Immunohistochemistry localized expression of HO-1 protein to vascular smooth muscle, whereas HO-2 was only detected in endothelium. HO-2 is expressed by aortic endothelial cells early during hypoxic exposure and impairs ET-1-mediated potentiation of contraction to -adrenoceptor stimulation.

vascular reactivity; oxygen delivery; blood flow regulation

This article has been cited by other articles:

				N. G. Abraham, J. Cao, D. Sacerdoti, X. Li, and G. Drummond Heme oxygenase: the key to renal function regulation Am J Physiol Renal Physiol, November 1, 2009; 297(5): F1137 - F1152. [Abstract] [Full Text] [PDF]

				J. Z. He, A. Quan, Y. Xu, H. Teoh, G. Wang, J. E. Fish, B. M. Steer, S. Itohara, P. A. Marsden, S. T. Davidge, et al. Induction of matrix metalloproteinase-2 enhances systemic arterial contraction after hypoxia Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H684 - H693. [Abstract] [Full Text] [PDF]

				A. I. Goodman, P. N. Chander, R. Rezzani, M. L. Schwartzman, R. F. Regan, L. Rodella, S. Turkseven, E. A. Lianos, P. A. Dennery, and N. G. Abraham Heme Oxygenase-2 Deficiency Contributes to Diabetes-Mediated Increase in Superoxide Anion and Renal Dysfunction J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1073 - 1081. [Abstract] [Full Text] [PDF]