ABSTRACT
Nitric oxide-dependent relaxation is decreased by atherosclerosis disease in both man and animal models of disease. Increased superoxide levels may contribute by decreasing the bioavailability of nitric oxide. The effects of oxidative stress and increased pro duction of superoxide anions on endothelium-dependent hyperpolarizing factor is less clear. The present experiments were designed to compare the effects of superoxide anions and another potentially harmful species, hydrogen peroxide, on endotheliumdependent relaxations in human arteries used in coronary artery bypass graft surgery. Relaxation of isolated rings of artery to carbachol was studied in organ chambers before and after addition of superoxide dismutase and catalase. Superoxide anions levels in the arteries were measured using lucigenin chemiluminescence. The endogenous levels of superoxide anions were similar in internal mammary and radial arteries. In internal mammary artery no relaxation to carbachol was observed in the presence of the inhibitor of nitric oxide synthase N G -nitro-L-arginine methyl ester ( L - N A M E ) . The nitric oxide-dependent relaxation was enhanced in the presence of superoxide dismutase. In radial arteries, both nitric oxide-dependent and independent relaxations to carbachol were observed. Superoxide dismutase and the polyethylene glycolated form of the enzyme both enhanced the nitric oxide-dependent but not the nitric oxide independent relaxation. Catalase had no effect on relaxations to carbachol either in the presence or absence of L - N A M E . These results suggest that nitric oxide dependent relaxation to carbachol is attenuated by superoxide in internal mammary and radial arteries. In radial arteries, nitric oxide-independent relaxation to carbachol is also observed which appears not to be modified by superoxide or hydrogen peroxide. Resistance to oxidative stress could contribute to long term patency of radial arteries used in revascularization surgery.
