EFFECTS OF A XANTHINE-OXIDASE HYPOXANTHINE FREE-RADICAL AND REACTIVE OXYGEN SPECIES GENERATING-SYSTEM ON ENDOTHELIAL FUNCTION IN NEW-ZEALAND WHITE-RABBIT AORTIC RINGS

We investigated the effects of the xanthine oxidase (XO)/hypoxanthine (HX) free radical (FR) generating system on the relaxant properties of aortic rings from New Zealand White rabbits. This system generates su peroxide anions, hydroxyl radicals, and H2O2. We wished to identify wh ich of these species is responsible for impairment of vascular functio n. After obtaining dose-response curves to phenylephrine (PE) and carb achol or sodium nitroprusside (SNP), we exposed rings to the FR genera ting system or H2O2 for 30 min, either with or without a range of pote ntially protective agents. Dose-response curves to carbachol or SNP we re then repeated. Exposure to the XO/HX system impaired endothelium-de pendent, carbachol-induced relaxation. The hydroxyl radical scavengers mannitol, N-(2-mercaptopropionyl)-glycine (MPG), and captopril offere d no protection. Superoxide dismutase (SOD) increased the impairment o f response, catalase provided partial protection, and a combination of SOD and catalase completely prevented impairment of the response. H2O 2 mimicked the effects of XO/HX system. H2O2 appears to be the primary species involved in mediating the toxic effects of the XO/HX FR gener ating system, but the superoxide anion is probably responsible for som e of the loss of relaxation and a role for intracellular generation of hydroxyl radicals cannot be excluded.