Cachofeiro V, Nasjletti A
Department of Pharmacology, New York Medical College, Valhalla 10595.
Hypertension. 1991 Nov;18(5):683-8. doi: 10.1161/01.hyp.18.5.683.
We investigated the role of nitric oxide (NO)-dependent and NO-independent mechanisms in mediation of renal vasodilatory responses to bradykinin in spontaneously hypertensive rats (SHR), rats with angiotensin II-induced hypertension (200 ng/min i.p. for 6 days) and the corresponding normotensive control Wistar-Kyoto (WKY) rats and sham-infused rats. To this end, we contrasted the effects of arterial injections of bradykinin and other vasodilators, acetylcholine and sodium nitroprusside, on perfusion pressure and output of cyclic GMP in isolated kidneys perfused with Krebs bicarbonate buffer containing phenylephrine, both with and without N omega-nitro-L-arginine (L-NOARG) (50 microM), an inhibitor of NO synthetase. In kidneys perfused without L-NOARG, all agonists increased the output of cyclic GMP and reduced perfusion pressure, indicative of vasodilation. In kidneys perfused with L-NOARG, vasodilatory responses to bradykinin and acetylcholine were attenuated, and associated effects on output of cyclic GMP were abolished, suggesting dependency on NO synthesis. Irrespective of whether kidneys were perfused with or without L-NOARG, kidneys of SHR were more responsive than kidneys of WKY rats with regard to bradykinin-induced vasodilation. In contrast, vasodilatory responsiveness to bradykinin was nearly equal in perfused kidneys of rats with angiotensin II-induced hypertension and in normotensive controls. Also, vasodilatory responsiveness to acetylcholine and sodium nitroprusside was similar in kidneys of normotensive and hypertensive rats. These data suggest that the renal vasculature of SHR is uniquely and selectively hyperresponsive to bradykinin, with regard to both the NO-dependent and NO-independent vasodilatory actions.
我们研究了一氧化氮（NO）依赖性和非NO依赖性机制在自发性高血压大鼠（SHR）、血管紧张素II诱导的高血压大鼠（腹腔注射200 ng/min，持续6天）以及相应的正常血压对照Wistar-Kyoto（WKY）大鼠和假灌注大鼠中介导肾脏对缓激肽血管舒张反应的作用。为此，我们对比了动脉注射缓激肽和其他血管舒张剂（乙酰胆碱和硝普钠）对用含去氧肾上腺素的 Krebs 碳酸氢盐缓冲液灌注的离体肾脏灌注压力和环磷酸鸟苷（cGMP）输出的影响，灌注过程中分别添加和不添加 NO 合酶抑制剂 Nω-硝基-L-精氨酸（L-NOARG，50 μM）。在未添加 L-NOARG 灌注的肾脏中，所有激动剂均增加了 cGMP 的输出并降低了灌注压力，表明血管舒张。在添加 L-NOARG 灌注的肾脏中，对缓激肽和乙酰胆碱的血管舒张反应减弱，并且对 cGMP 输出的相关影响被消除，提示依赖于 NO 合成。无论肾脏是否用 L-NOARG 灌注，SHR 的肾脏对缓激肽诱导的血管舒张反应比 WKY 大鼠的肾脏更敏感。相比之下，血管紧张素II诱导的高血压大鼠灌注肾脏和正常血压对照大鼠对缓激肽的血管舒张反应性几乎相等。此外，正常血压和高血压大鼠肾脏对乙酰胆碱和硝普钠的血管舒张反应性相似。这些数据表明，就NO依赖性和非NO依赖性血管舒张作用而言，SHR的肾血管系统对缓激肽具有独特且选择性的高反应性。
