Inhibition of nitric oxide synthase by a superoxide generating system.

Although superoxide anion is known to inactivate nitric oxide (NO) once formed, its effect on NO synthesis is unclear. In this study, xanthine oxidase-hypoxanthine, a superoxide anion generating system, inhibited bovine cerebellum NO synthase activity as measured by the conversion of L-[3H]arginine to L-[3H]citrulline. This inhibition by xanthine oxidase was concentration-dependent. Superoxide dismutase-catalase and allopurinol, an inhibitor of xanthine oxidase, attenuated in part the inhibition of NO synthase activity by xanthine oxidase. Xanthine oxidase also produced a decrease in the partial pressure of oxygen in the assay mixture. The inhibition of NO synthase activity by xanthine oxidase was reversed completely when oxygen was passed continuously through the reaction mixture. This study suggests that a decrease in oxygen concentration caused by superoxide generation may inhibit NO synthesis.