Effect of xanthine oxidase inhibition on endothelium-dependent and nitrergic relaxations

The effects of inhibition of xanthine oxidase on responses mediated by nitric oxide (NO) were examined using the selective xanthine oxidase inhibitors allopurinol and 4-amino-6-hydroxypyrazolo[3,4-d]pyrimidine (AHPP). In rat aortic rings precontracted with phenylephrine (1 microM), allopurinol (300 microM) and AHPP (100, 300 microM) significantly reduced tone, an effect not seen after inhibition of NO synthase with Nomega-nitro-L-arginine (NOLA 100 microM). Relaxations produced by acetylcholine (0.01-10 microM) were significantly enhanced by AHPP (100, 300 microM) but not by allopurinol. Nitrergic relaxations in the rat anococcygeus muscle (field stimulation 1 ms pulses; 1 Hz: 10 s) were not affected by either allopurinol or AHPP. However, relaxations produced by exogenous NO (0.25 microM) were significantly enhanced by AHPP, allopurinol (100 microM) and superoxide dismutase (100 U/ml). Xanthine (500 microM) partially, but significantly, reversed the enhancement produced by AHPP. These findings suggest that superoxide generated by xanthine oxidase modulates the activity of basal and stimulated NO derived from the rat aortic endothelium, but does not affect the activity of the nitrergic transmitter in the rat anococcygeus muscle, despite its ability to modulate responses to exogenous NO.