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 mu M), allopurinol (300 mu M) and AHPP (100, 300 mu M) significantly reduced tone, an effect not seen after inhibition of NO synthase with N-omega-nitro-L-arginine (NOLA 100 mu M). Relaxations produced by acetylcholine (0.01-10 mu M) were significantly enhanced by AHPP (100, 300 mu M) 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 mu M) were significantly enhanced by AHPP, allopurinol (100 mu M) and superoxide dismutase (100 U/ml). Xanthine (500 mu M) 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. (C) 1998 Elsevier Science B.V. All rights reserved.