Ellis A, Li C G, Rand M J
Department of Medical Laboratory Science, Royal Melbourne Institute of Technology, Vic, Australia.
Eur J Pharmacol. 1998 Aug 28;356(1):41-7. doi: 10.1016/s0014-2999(98)00510-x.
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.
使用选择性黄嘌呤氧化酶抑制剂别嘌呤醇和4-氨基-6-羟基吡唑并[3,4-d]嘧啶（AHPP），研究了抑制黄嘌呤氧化酶对一氧化氮（NO）介导反应的影响。在预先用去氧肾上腺素（1微摩尔）收缩的大鼠主动脉环中，别嘌呤醇（300微摩尔）和AHPP（100、300微摩尔）显著降低张力，而用Nω-硝基-L-精氨酸（NOLA 100微摩尔）抑制一氧化氮合酶后未观察到这种效应。AHPP（100、300微摩尔）可显著增强乙酰胆碱（0.01 - 10微摩尔）产生的舒张作用，但别嘌呤醇无此作用。别嘌呤醇或AHPP均不影响大鼠肛门尾骨肌中的氮能舒张（场刺激1毫秒脉冲；1赫兹：10秒）。然而，AHPP、别嘌呤醇（100微摩尔）和超氧化物歧化酶（100单位/毫升）可显著增强外源性NO（0.25微摩尔）产生的舒张作用。黄嘌呤（500微摩尔）部分但显著地逆转了AHPP产生的增强作用。这些发现表明，黄嘌呤氧化酶产生的超氧化物调节大鼠主动脉内皮衍生的基础和刺激型NO的活性，但尽管其能够调节对外源性NO的反应，却不影响大鼠肛门尾骨肌中氮能递质的活性。
