Division of Gastroenterology, Gradenigo Hospital, Torino, Italy.
J Hepatol. 2010 Nov;53(5):856-62. doi: 10.1016/j.jhep.2010.05.021. Epub 2010 Jul 24.
BACKGROUND & AIMS: Extracellular Ca(++) activates cell membrane calcium-sensing receptors (CaRs), leading to renal tubule production of prostaglandins E(2) (PGE(2)), which decrease both sodium reabsorption in the thick ascending limb of Henle's loop and free-water reabsorption in collecting ducts.
AIMS & METHODS: To assess the activity of this diuretic system in experimental cirrhosis, we evaluated renal function, hormonal status, PGE(2) urinary excretion, and renal tissue concentrations of Na(+)-K(+)-2Cl(-) co-transporters (BSC-1) and CaRs in three groups of rats: one group of controls receiving 5% glucose solution (vehicle) intravenously and two groups of rats with CCl(4)-induced preascitic cirrhosis receiving either vehicle or 0.5mg i.v. Poly-l-Arginine (PolyAg), a CaR-selective agonist.
Compared to controls, cirrhotic rats showed reduced urine volume and sodium excretion (p<0.05). Western blot analysis revealed reduced CaRs and increased BSC-1 protein content in kidneys of cirrhotic rats compared with controls (all p<0.01). PolyAg-treated cirrhotic rats had their urine and sodium excretion returned to normal; PolyAg also increased renal plasma flow, PGE(2) urinary excretion, and free-water clearance in cirrhotic rats (all p<0.01 v. untreated cirrhotic animals).
In preascitic cirrhosis, sodium retention may be linked to down-regulation of renal CaRs and up-regulation of tubular sodium-retaining channels. Calcimimetic drugs normalize preascitic sodium retention.
细胞外钙（++）激活细胞膜钙敏感受体（CaR），导致肾脏远曲小管产生前列腺素 E2（PGE2），减少亨利氏袢升支粗段的钠离子重吸收和集合管的游离水重吸收。
为了评估该利尿系统在实验性肝硬化中的活性，我们评估了肾功能、激素状态、PGE2 尿排泄和肾脏组织中 Na+-K+-2Cl-共转运体（BSC-1）和 CaR 的浓度，分为三组大鼠：一组接受 5%葡萄糖溶液（载体）静脉内注射，两组 CCl4 诱导的腹水前肝硬化大鼠分别接受载体或 0.5mg 静脉内聚精氨酸（PolyAg），一种 CaR 选择性激动剂。
与对照组相比，肝硬化大鼠的尿量和钠排泄减少（p<0.05）。Western blot 分析显示，与对照组相比，肝硬化大鼠肾脏中的 CaR 和 BSC-1 蛋白含量减少（均 p<0.01）。PolyAg 治疗的肝硬化大鼠的尿液和钠排泄恢复正常；PolyAg 还增加了肝硬化大鼠的肾血浆流量、PGE2 尿排泄和游离水清除率（均 p<0.01 比未治疗的肝硬化动物）。
在腹水前肝硬化中，钠潴留可能与肾脏 CaR 下调和管状钠保留通道上调有关。钙敏感受体药物可使腹水前的钠潴留正常化。
