Calcium-dependent diuretic system in preascitic liver cirrhosis.

Background & Aims: Extracellular Ca++ activates cell membrane calcium-sensing receptors (CaRs), leading to renal tubule production of prostaglandins E2 (PGE2), 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, PGE2 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 CCl4-induced preascitic cirrhosis receiving either vehicle or 0.5 mg i.v. Poly-L-Arginine (PolyAg), a CaR-selective agonist. Results: 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, PGE2 urinary excretion, and free-water clearance in cirrhotic rats (all p <0.01 v. untreated cirrhotic animals).