Bech Jesper N, Aagaard Niels K, Pedersen Robert S, Sorensen Tina B, Vilstrup Hendrik, Pedersen Erling B
Department of Medical Research, Holstebro Hospital, Holstebro Denmark and Aarhus University, Aarhus, Denmark; Department of Medicine, Holstebro Hospital, Holstebro, Denmark.
Liver Int. 2014 Feb;34(2):211-9. doi: 10.1111/liv.12233. Epub 2013 Jun 28.
Nitric oxide (NO) is an important regulator of renal hemodynamics and sodium excretion. Systemic and splanchnic NO-synthesis is increased in liver cirrhosis contributing to the characteristic hyperdynamic circulation. The significance of renal NO in human cirrhosis is not clear.
In order to clarify the role of NO in the regulation of renal hemodynamics and sodium excretion in human cirrhosis, we studied the effects of N(G)-monomethyl-L-arginine (L-NMMA) - a nonselective NO-inhibitor - on blood pressure (MAP), heart rate (HR), GFR, RPF, UNa × V, FENa, FELi and plasma levels of renin, angII, aldo, ANP, BNP and cGMP in 13 patients with cirrhosis (Child gr.A: 8; Child gr.B+C: 5) and 13 healthy controls.
The study was randomized and placebo-controlled. Renal hemodynamics were assessed by measuring renal clearance of (51) Cr-EDTA and (125) I-Hippuran for GFR and RPF, respectively.
L-NMMA induced a similar, significant increase in MAP in both groups and a more pronounced relative decrease in HR in the CIR group (P = 0.0209, anova). L-NMMA did not change GFR in any group, but RPF decreased significantly in both groups, but most pronouncedly in CIR (P = 0.0478, anova). FENa decreased significantly in both groups after l-NMMA, but the response was again most pronounced in the CIR group (P = 0.0270, anova). All parameters remained stable after placebo. No significant differences were observed between the effects of L-NMMA in Child gr.A vs. Child gr. B+C patients.
The data supports the hypothesis that renal NO is enhanced in human cirrhosis.
一氧化氮（NO）是肾血流动力学和钠排泄的重要调节因子。肝硬化时全身和内脏NO合成增加，导致特征性的高动力循环。肾NO在人类肝硬化中的意义尚不清楚。
为了阐明NO在人类肝硬化肾血流动力学和钠排泄调节中的作用，我们研究了N（G）-单甲基-L-精氨酸（L-NMMA）——一种非选择性NO抑制剂——对13例肝硬化患者（Child A级：8例；Child B + C级：5例）和13例健康对照者的血压（MAP）、心率（HR）、肾小球滤过率（GFR）、肾血浆流量（RPF）、尿钠×尿量（UNa×V）、滤过钠分数（FENa）、滤过锂分数（FELi）以及肾素、血管紧张素II、醛固酮、心房钠尿肽（ANP）、脑钠肽（BNP）和环磷酸鸟苷（cGMP）血浆水平的影响。
本研究为随机、安慰剂对照试验。分别通过测量（51）Cr-乙二胺四乙酸（EDTA）和（125）I-马尿酸的肾清除率来评估肾血流动力学，以测定GFR和RPF。
L-NMMA使两组的MAP均出现相似的显著升高，且使肝硬化组（CIR组）的HR相对下降更为明显（P = 0.0209，方差分析）。L-NMMA未改变任何一组的GFR，但两组的RPF均显著下降，不过在CIR组最为明显（P = 0.0478，方差分析）。L-NMMA给药后两组的FENa均显著下降，但同样在CIR组反应最为明显（P = 0.0270，方差分析）。安慰剂给药后所有参数均保持稳定。L-NMMA对Child A级患者和Child B + C级患者的影响之间未观察到显著差异。
数据支持人类肝硬化时肾NO增强的假说。
Zotero 插件