Free radical involvement in endothelium-dependent responses of the rat thoracic aorta in moderate hypoxic conditions.

This study investigates the effects of agents which act on the production or efficacy of free radicals on the hypoxic responses of rat aorta rings. Under moderate hypoxic conditions, the resting tension of the rings was not changed but in rings precontracted with 5-hydroxytryptamine, there was a relaxation followed by a contraction. Removal of the endothelium with saponin suppressed relaxation to acetylcholine and abolished the contractions produced by hypoxia. In rings with a functional endothelium, hypoxic vasoconstriction was strongly inhibited by mannitol and exifone, but was not reduced by N(G)-nitro-L-arginine methyl ester, superoxide dismutase + catalase, or deferoxamine. Hypoxic vasodilatation was only partially inhibited by mannitol. To conclude, hypoxic constriction of the rat thoracic aorta is largely endothelium-dependent and involves free radicals whereas hypoxic dilatation is partially endothelium-dependent and partially involves free radicals. There is also indirect evidence for lack of direct involvement of nitric oxide/endothelium-derived relaxing factor (NO*/EDRF), hydroxyl radical (OH*) and superoxide anion in the hypoxic constriction and relaxation of the rat aorta.