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Am J Physiol Heart Circ Physiol (November 21, 2002). doi:10.1152/ajpheart.00747.2002
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Articles in PresS, published online ahead of print November 21, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00747.2002
Submitted on August 28, 2002
Accepted on November 12, 2002

Endogenous Carbon Monoxide is an Endothelial-Derived Vasodilator Factor in the Mesenteric Circulation

Jay S. Naik1, Theresa L. O'Donaughy1, and Benjimen R. Walker1*

1 Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

* To whom correspondence should be addressed. E-mail: bwalker{at}salud.unm.edu.

Chronic hypoxia (CH) is associated with both blunted agonist-induced and myogenic vascular reactivity, possibly due to an enhanced production of heme oxygenase (HO) derived carbon monoxide (CO). However, the cellular location of the HO responsible for these effects has not been clearly established. Therefore, we examined the response to administration of the substrate for HO, heme-L-lysinate (HLL) in endothelium-intact and endothelium-denuded small mesenteric arteries from CH male Sprague-Dawley rats. Mesenteric arteries were isolated and mounted on glass cannulae, pressurized to 60 mmHg and superfused with PSS. All experiments were performed in the presence of 100 µM N{omega}-nitro-L-arginine. The vasodilatory response to HLL or exogenous CO was examined. HLL experiments were performed in the presence and absence of the HO inhibitor, ZnPPIX. HLL administration resulted in a dose-dependent vasodilatory response, which was abolished in the presence of ZnPPIX or by endothelial removal. Exogenous CO produced a vasodilator response that was independent of an intact endothelium. Cellular localization of HO was verified through immunohistochemistry in sections of gut and aorta from CH and control animals. Staining for HO-1, HO-2 and endothelial nitric oxide synthase (eNOS) was confined to the endothelium. Thus, we conclude that CO is a product of HO located within the endothelium.




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