RATIONALE: Hypoxic pulmonary vasoconstriction (HPV) is an important mechanism by which pulmonary gas exchange is optimized by the adaptation of blood flow to alveolar ventilation. In chronic hypoxia, in addition to HPV a vascular remodeling process leads to pulmonary hypertension. Recently, a complex of heme oxygenase-2 (HO-2) and the BK channel has been suggested as a universal oxygen sensor system. OBJECTIVE: We investigated, whether this complex serves as an oxygen sensor for the vascular effects of alveolar hypoxia in the lung. METHODS and RESULTS: Immunohistochemical analysis of mouse lungs identified HO-2 mainly in pulmonary arteries, the bronchial epithelium and alveolar epithelial cells. BK channel -subunit (BK) immunoreactivity was found primarily in the bronchial and vascular smooth muscle layer. Immunofluorescence staining and co-immunoprecipitation suggested only a weak complexation of HO-2 and BK in pulmonary arterial smooth muscle cells. The strength of acute and sustained HPV, determined in isolated perfused and ventilated lungs, was not different between the wild-type, HO-2- and BK-deficient mice. Exposure of mice to three weeks of chronic hypoxia resulted in a slight downregulation of HO-2 and no alteration in BK expression. The degree of pulmonary hypertension which developed, quantified from right ventricular pressure, right heart hypertrophy, and the degree of muscularization of precapillary pulmonary arteries, was not different between the wild-type, HO-2- or BK-deficient mice. CONCLUSION: It is demonstrated that neither deletion of HO-2 nor BK channels affects the acute, sustained and chronic vascular responses to alveolar hypoxia in the lung.