Wolzt M, Schmetterer L, Ferber W, Artner E, Mensik C, Eichler H G, Krejcy K
Department of Clinical Pharmacology, Vienna University, Austria.
Am J Physiol. 1997 Feb;272(2 Pt 2):F178-82. doi: 10.1152/ajprenal.1997.272.2.F178.
Animal experiments indicate that inhibition of nitric oxide synthase (NOS) influences renal hemodynamics and that this effect can be reversed by L-arginine, the precursor of NO synthesis. We have therefore studied the effects of an inhibitor of NOS, N(G)-monomethyl-L-arginine (L-NMMA), and a subsequent coinfusion with L-arginine on renal hemodynamics. In a double-blind, randomized crossover design, eight healthy volunteers (means +/- 1SD, 25.6 +/- 3.1 yr) received a primed constant infusion of L-NMMA (3 mg/kg bolus infusion over 5 min, followed by 50 microg x kg(-1) x min(-1) over 120 min) with subsequent coinfusion of L-arginine (17 mg x kg(-1) x min(-1) over 30 min). In the absence of a hypertensive response, L-NMMA decreased renal plasma flow to 79% of baseline (P < 0.005); this effect was abrogated by L-arginine. Glomerular filtration rate was not affected, NO exhalation was reduced to 30% of baseline (P < 0.005) by L-NMMA, and this effect was attenuated by L-arginine. Our results demonstrate that basal NO production maintains renal blood flow in vivo in humans. In addition, the renal vasculature is particularly sensitive to inhibition of NOS, and these pharmacodynamic effects can be reversed by excess doses of L-arginine.
动物实验表明，一氧化氮合酶（NOS）的抑制会影响肾血流动力学，并且这种效应可被L-精氨酸（NO合成的前体）逆转。因此，我们研究了NOS抑制剂N(G)-单甲基-L-精氨酸（L-NMMA）以及随后与L-精氨酸共同输注对肾血流动力学的影响。在双盲、随机交叉设计中，8名健康志愿者（平均年龄±1标准差，25.6±3.1岁）接受了L-NMMA的首剂持续输注（5分钟内静脉推注3mg/kg，随后120分钟内以50μg·kg⁻¹·min⁻¹持续输注），随后共同输注L-精氨酸（30分钟内以17mg·kg⁻¹·min⁻¹持续输注）。在无高血压反应的情况下，L-NMMA使肾血浆流量降至基线的79%（P<0.005）；这种效应被L-精氨酸消除。肾小球滤过率未受影响，L-NMMA使NO呼出量降至基线的30%（P<0.005），且这种效应被L-精氨酸减弱。我们的结果表明，基础NO生成在人体内维持肾血流量。此外，肾血管系统对NOS抑制特别敏感，且这些药效学效应可被过量的L-精氨酸逆转。
