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This Article Full Text Full Text (PDF) All Versions of this Article: 286/1/H137    most recent 00678.2002v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Zhang, F. Articles by Nasjletti, A. Search for Related Content PubMed PubMed Citation Articles by Zhang, F. Articles by Nasjletti, A.

CO modulates pulmonary vascular response to acute hypoxia: relation to endothelin

Department of Pharmacology, New York Medical College, Valhalla, New York 10595

Submitted 31 July 2003 ; accepted in final form 3 September 2003

Pulmonary intralobar arteries express heme oxygenase (HO)-1 and -2 and release carbon monoxide (CO) during incubation in Krebs buffer. Acute hypoxia elicits isometric tension development (0.77 ± 0.06 mN/mm) in pulmonary vascular rings treated with 15 µmol/l chromium mesoporphyrin (CrMP), an inhibitor of HO-dependent CO synthesis, but has no effect in untreated vessels. Acute hypoxia also induces contraction of pulmonary vessels taken from rats injected with HO-2 antisense oligodeoxynucleotides (ODN), which decrease pulmonary HO-2 vascular expression and CO release. Hypoxia-induced contraction of vessels treated with CrMP is attenuated (P < 0.05) by endothelium removal, by CO (1–100 µmol/l) in the bathing buffer, and by endothelin-1 (ET-1) receptor blockade with L-754142 (10 µmol/l). CrMP increases ET-1 levels in pulmonary intralobar arteries, particularly during incubation in hypooxygenated media. CrMP also causes a leftward shift in the concentration-response curve to ET-1, which is offset by exogenous CO. In anesthetized rats, pretreatment with CrMP (40 µmol/kg iv) intensifies the elevation of pulmonary artery pressure elicited by breathing a hypoxic gas mixture. However, acute hypoxia does not elicit augmentation of pulmonary arterial pressure in rats pretreated concurrently with CrMP and the ET-1 receptor antagonist L-745142 (15 mg/kg iv). These data suggest that a product of HO activity, most likely CO, inhibits hypoxia-induced pulmonary vasoconstriction by reducing ET-1 vascular levels and sensitivity.

hypoxic pulmonary vasoconstriction; heme oxygenase