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Invited Symposium: Carbon Monoxide and Cardiovascular Function






Abstract

Introduction

Materials & Methods

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Heme Oxygenase and CO Actions in Blood Vessels

Nakatsu, K. (Department of Pharmacology and Toxicology, Queen's University, Canada)
Brien, J.F. (Department of Pharmacology and Toxicology, Queen's University, Canada)
Graham, C.H. (Department of Anatomy and Cell Biology, Queen's University, Canada)
McLaughlin, B.E. (Department of Pharmacology and Toxicology, Queen's University, Canada)
Hussain, A.S. (Department of Pharmacology and Toxicology, Queen's University, Canada)
Odrcich, M.J. (Department of Pharmacology and Toxicology, Queen's University, Canada)
Marks, G.S. (Department of Pharmacology and Toxicology, Queen's University, Canada)

Contact Person: Kanji Nakatsu (nakatsuk@post.queensu.ca)


Abstract

It has been proposed that carbon monoxide (CO) acts as a vasodilator by activating soluble guanylyl cyclase (GC). To test this, we determined the effect of the GC inhibitor,ODQ (1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), on CO-induced relaxation of rabbit aorta. In isolated ring preparations, relaxation to CO (30 uM) was abolished by 10 uM ODQ whereas 0.1 and 1 uM ODQ caused approximately 40% and 90% decreases in relaxation, respectively. For CO to be considered as an endogenous regulator of vascular tone, a mechanism for its synthesis in blood vessels must be identified. Accordingly, we have used polyclonal antibodies for heme oxygenase (isozymes, HO-1 and HO-2) to localize this enzyme, which forms CO during the degradation of heme, in bovine pulmonary artery and vein, and in guinea pig and human placenta. HO protein was localized in the adventitial, medial and intimal layers of bovine pulmonary artery and vein, and in the adventitia of fetal blood vessels of guinea pig and human placenta. In addition the formation of CO as a result of HO activity was measured in bovine pulmonary artery and vein and in guinea pig placenta. These observations are consistent with a functional role for CO in the regulation of the mechanical activity of blood vessels. This work was supported by the Heart and Stroke Foundation of Ontario and the Medical Research Council of Canada

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Presentation Number SAnakatsu0681
Keywords: carbon monoxide, vasodilator, isolated tissues, ODQ, heme oxygenase


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Nakatsu, K.; Brien, J.F.; Graham, C.H.; McLaughlin, B.E.; Hussain, A.S.; Odrcich, M.J.; Marks, G.S.; (1998). Heme Oxygenase and CO Actions in Blood Vessels. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/wang/nakatsu0681/index.html
© 1998 Author(s) Hold Copyright