Nishiyama A, Miyatake A, Kusudo K, Syokoji T, Yue W, Fukui T, Aki Y, Kimura S, Abe Y
Department of Pharmacology, Kagawa Medical University, Japan.
Eur J Pharmacol. 1999 Feb 19;367(2-3):299-306. doi: 10.1016/s0014-2999(98)00978-9.
The effects of halothane on renal hemodynamics and the nitric oxide (NO)-guanylate cyclase signaling pathway were examined in anesthetized rabbits using a renal microdialysis method. Halothane (0.5 and 2 vol%) caused dose-dependent decreases in blood pressure, renal blood flow and the renal interstitial concentrations of guanosine 3',5'-cyclic monophosphate (cGMP) or nitrate (NO2)/nitrite (NO3). Sodium nitroprusside (20 microg kg(-1) min(-1), i.v.) under the inhalation of halothane (2 vol%) increased the renal interstitial concentration of cGMP. L-Arginine (priming dose, 300 mg kg(-1) 10 min(-1); sustaining dose, 50 mg kg(-1) min(-1), i.v.) did not reverse halothane-induced reductions of cGMP and NO2/NO3. These findings demonstrate that halothane caused a renal vasoconstriction and inhibited the NO-guanylate cyclase signaling pathway in the kidney. Moreover, it is possible that the renal hemodynamic responses to halothane might have been induced, in part, through this inhibition. Finally, it can be assumed that halothane did not interfere with the activation process of guanylate cyclase by NO.
采用肾微透析法，在麻醉兔中研究了氟烷对肾血流动力学及一氧化氮（NO）-鸟苷酸环化酶信号通路的影响。氟烷（0.5%和2%体积分数）使血压、肾血流量以及肾间质中环磷酸鸟苷（cGMP）或硝酸盐（NO₂）/亚硝酸盐（NO₃）的浓度呈剂量依赖性降低。在吸入2%体积分数氟烷的情况下，硝普钠（20 μg·kg⁻¹·min⁻¹，静脉注射）可提高肾间质cGMP浓度。L-精氨酸（首剂，300 mg·kg⁻¹·10 min⁻¹；维持剂量，50 mg·kg⁻¹·min⁻¹，静脉注射）不能逆转氟烷引起的cGMP和NO₂/NO₃降低。这些结果表明，氟烷引起肾血管收缩并抑制肾内的NO-鸟苷酸环化酶信号通路。此外，氟烷对肾血流动力学的反应可能部分是通过这种抑制作用诱导的。最后，可以推测氟烷不会干扰NO对鸟苷酸环化酶的激活过程。
