Oxygen radicals and antioxidant enzymes alter pulmonary vascular reactivity in the rat lung

It has been postulated that changes in the availability of partially reduced O₂ species, such as O₂ radicals, could serve as a link between PO₂ in the alveolus and pulmonary vascular tone (Herz 11: 127-141, 1986). To assess this hypothesis, the hemodynamic effects of acute changes in the balance between the production of O₂ radicals and availability of antioxidant enzymes were studied in the isolated perfused rat lung. Intravascular generation of O₂ radicals, by administration of xanthine-xanthine oxidase, decreased the pulmonary vascular pressor response to alveolar hypoxia (-55 ± 5%) and angiotensin II (-58 ± 10%, P<0.01 for each) in isolated perfused rat lungs without increasing the lung wet-to-dry weight ratio. Decreases in pulmonary vascular reactivity were inhibited by pretreatment of the lung with desferrioxamine or a mixture of catalase and superoxide dismutase. Catalase and superoxide dismutase preserved the hypoxic pressor response whether given in liposomes or in dissolved form. Superoxide dismutase administered free in solution, or combined with catalase in liposomes, increased the normoxic pulmonary arterial pressure and enhanced vascular reactivity to angiotensin II and hypoxia. Lungs treated with antioxidant enzymes in liposomes had 50% higher lung catalase levels than control lungs (P<0.05). These findings demonstrate that exogenous partially reduced O₂ species can decrease pulmonary vascular reactivity and suggest that endogenous radicals, superoxide radical in particular, might be important in modulating pulmonary vascular tone.