Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor.
Experiments were designed to determine the effects of oxygen-derived free radicals on the production and biological activity of endothelium-derived relaxing factor or factors released by acetylcholine. Rings of canine coronary arteries without endothelium (bioassay rings) were superfused with solution passing through a canine femoral artery with endothelium. Superoxide dismutase caused maximal relaxation of the bioassay ring when infused upstream, but not downstream, of the femoral artery; this effect of superoxide dismutase was inhibited by catalase. Infusion of acetylcholine relaxed the bioassay rings because it released a labile relaxing factor (or factors) from the endothelium. When infused below the femoral artery, superoxide dismutase and, to a lesser extent, catalase augmented the relaxations to acetylcholine. Superoxide dismutase, but not catalase, doubled the half-life of the endothelium-derived relaxing factor(s). This protective effect of the enzyme was augmented fivefold by lowering the oxygen content of the perfusate from 95 to 10%. These data demonstrate that: superoxide anions inactivate the relaxing factor(s) released by acetylcholine from endothelial cells and hyperoxia favors the inactivation of endothelium-derived relaxing factor(s).
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D006207:Half-Life; D008297:Male; D009569:Nitric Oxide; D010100:Oxygen / Q000097:blood* / Q000494:pharmacology; D010827:Physiology / Q000295:instrumentation; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology*; D013997:Time Factors; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors*
D000838:Anions; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D002374:Catalase; D013482:Superoxide Dismutase; D000109:Acetylcholine; D010100:Oxygen