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 o r efficacy of free radicals on the hypoxic responses of rat aorta rings. Un der moderate hypoxic conditions, the resting tension of the rings was not c hanged but in rings precontracted with 5-hydroxytryptamine, there was a rel axation followed by a contraction. Removal of the endothelium with saponin suppressed relaxation to acetylcholine and abolished the contractions produ ced by hypoxia. In rings with a functional endothelium, hypoxic vasoconstri ction was strongly inhibited by mannitol and exifone, but was not reduced b y N-G-nitro-L-arginine methyl ester, superoxide dismutase + catalase, or de feroxamine. Hypoxic vasodilatation was only partially inhibited by mannitol . To conclude, hypoxic constriction of the rat thoracic aorta is largely en dothelium-dependent and involves free radicals whereas hypoxic dilatation i s partially endothelium-dependent and partially involves free radicals. The re is also indirect evidence for lack of direct involvement of nitric oxide /endothelium-derived relaxing factor (NO degrees/EDRF), hydroxyl radical (O H degrees) and superoxide anion in the hypoxic constriction and relaxation of the rat aorta. (C) 1999 Elsevier Science B.V. All rights reserved.