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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/H1453    most recent 00315.2009v1 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 Google Scholar Articles by Ahmad, M. Articles by Wolin, M. S. PubMed PubMed Citation Articles by Ahmad, M. Articles by Wolin, M. S.

Heme oxygenase-1 induction modulates hypoxic pulmonary vasoconstriction through upregulation of ecSOD

Departments of ¹Physiology and ²Pharmacology, New York Medical College, Valhalla, New York

Submitted March 31, 2009 ; accepted in final form August 3, 2009

Endothelium-denuded bovine pulmonary arteries (BPA) contract to hypoxia through a mechanism potentially involving removing a superoxide-derived hydrogen peroxide-mediated relaxation. BPA organ cultured for 24 h with 0.1 mM cobalt chloride (CoCl₂) to increase the expression and activity of heme oxygenase-1 (HO-1) is accompanied by a decrease in 5 µM lucigenin-detectable superoxide and an increase in horseradish peroxidase-luminol detectable peroxide levels. Force development to KCl in BPA was not affected by increases in HO-1, but the hypoxic pulmonary vasoconstriction (HPV) response was decreased. Organ culture with a HO-1 inhibitor (10 µM chromium mesoporphyrin) reversed the effects of HO-1 on HPV and peroxide. Treatment of HO-1-induced BPA with extracellular catalase resulted in reversal of the attenuation of HPV without affecting the force development to KCl. Increasing intracellular peroxide scavenging with 0.1 mM ebselen increased force development to KCl and partially reversed the decrease in HPV seen on induction of HO-1. HO-1 induction increases extracellular (ec) superoxide dismutase (SOD) expression without changing Cu,Zn-SOD and Mn-SOD levels. HO-1-induced BPA rings treated with the copper chelator 10 mM diethyldithiocarbamate to inactivate ecSOD and Cu,Zn-SOD showed increased superoxide and decreased peroxide to levels equal to non-HO-1-induced rings, whereas the addition of SOD to freshly isolated BPA rings attenuated HPV similar to HO-1 induction with CoCl₂. Therefore, HO-1 induction in BPA increases ecSOD expression associated with enhanced generation of peroxide in amounts that may not be adequately removed during hypoxia, leading to an attenuation of HPV.

catalase; cobalt; hydrogen peroxide; superoxide; extracellular superoxide dismutase