Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites.
Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites.
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一氧化氮合酶 (NOS) 抑制一周可改善肝硬化腹水大鼠肾钠和水的排泄。
DOI：
10.1172/jci626
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Schrier,RW
中科院分区：
文献类型：
--
作者：
Martin,PY;Ohara,M;Gines,P;Xu,DL;StJohn,J;Niederberger,M;Schrier,RW
用低剂量的NG-硝基-L-精氨酸甲酯（L-NAME）使增加的血管一氧化氮（NO）生成正常化，纠正了腹水型糖尿病大鼠的血流动力学异常。我们进行了这项研究，以探讨血管NO生产的正常化的影响，估计主动脉环磷酸鸟苷（cGMP）浓度和内皮型一氧化氮合酶（eNOS）蛋白表达的主动脉和肠系膜动脉，钠和水的排泄。采用平衡研究法对四氯化碳诱导的肝硬化和腹水大鼠进行了研究。实验分为两组，一组给予L-NAME（CIR-NAME）0.5mg/kg/d，连续7 d，另一组给予等量的溶剂。另外两组大鼠用作对照，一组用L-NAME处理，另一组接受相同体积的载体。在第0天和第7天测量钠和水排泄。在第8天，收集血液样品用于电解质和激素测量，并且收获主动脉和肠系膜动脉用于cGMP测定和一氧化氮合酶（NOS）免疫印迹。与CIR-NAME组相比，CIR组主动脉和肠系膜动脉cGMP和eNOS蛋白表达均增加。两个糖尿病组在第0天的钠排泄量降低相似（0.7 vs 0.6 mmol/d，NS），并且钠平衡为正（+0.9 vs +1.2 mmol/d，NS）。在第7天，与CIR大鼠相比，CIR-NAME大鼠的钠排泄增加（钠排泄：2.4 vs 0.7 mmol/d，P < 0.001），并且钠平衡为负（-0.5 vs +0.8 mmol/d，P < 0.001）。给予L-NAME后，水负荷的排泄也增加（从28+/-5%增加到65+/-7，P < 0.05）。与CIR大鼠相比，CIR-NAME组血浆肾素活性、醛固酮和精氨酸加压素也显著降低。因此，结果表明，主动脉cGMP和eNOS蛋白在血管组织中的表达的正常化与腹水型糖尿病大鼠的钠和水排泄增加有关。
Normalization of the increased vascular nitric oxide (NO) generation with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and ascites were investigated using balance studies. The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L-NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administrated the same volume of vehicle. Two other groups of rats were used as controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7. On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus +1.2 mmol per day, NS). On day 7, CIR-NAME rats had an increase in sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate that normalization of aortic cGMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites.