title: Dynamics of sodium retention in preascitic cirrhotic rats assessed through parathyroid hormone injection.
abstract: Extracellular Ca(++) stimulates membrane-bound calcium-sensing receptors (CaRs). CaRs stimulation leads to PGE2-mediated decrease in protein content of Na(+)-K(+)-2Cl(-) co-transporters (BSC-1) in the thick ascending limb (TAL) of Henle's loop and of aquaporin 2 (AQP2) water channels in collecting ducts. Parathyroid hormone (PTH) increases CaRs and decreases BSC-1 and AQP2 tubular content. To assess the Ca(++)-dependent diuretic system in preascitic cirrhosis, we evaluated renal function, hormonal status, PGE2 urinary excretion, and renal content of BSC-1 and CaRs in three groups of rats: control rats received s.c. 5% glucose solution; two groups of rats with CCl4-induced preascitic cirrhosis received either s.c. glucose solution or five s.c. doses of 10 mcg/Kg PTH (one dose every 12 hours) prior to study. Cirrhotic rats, when compared to controls, showed reduced urine volume and sodium excretion; moreover, western blot analysis revealed reduced CaRs and increased BSC-1 protein content in cirrhotic rat kidneys. S.c. administration of PTH normalized urine and sodium excretion in cirrhotic rats and also increased renal plasma flow, PGE2 urinary excretion, and free-water clearance. Finally, PTH reduced BSC-1 and augmented CaRs content in cirrhotic rat kidneys. In conclusion, in preascitic cirrhosis sodium retention is associated with down-regulation of renal CaRs and up-regulation of tubular Na(+)-K(+)-2Cl(-) co-transporters. PTH returns these biomolecular changes, along with sodium and urine excretions, to normality, suggesting that exaggerated sodium reabsorption occurs primarily in the Henle's loop in preascitic cirrhosis.
authors.affiliation: Division of Gastroenterology, Gradenigo Hospital, Torino, Italy. giovannisan@iol.it.
authors.forename: G
authors.initials: G
authors.lastname: Sansoe
authors.forename: R
authors.initials: R
authors.lastname: Mastrocola
authors.forename: M
authors.initials: M
authors.lastname: Aragno
authors.forename: M
authors.initials: M
authors.lastname: Parola
mesh_terms: D000818:Animals; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1 / Q000378:metabolism*
chemical_list: D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; C578716:Slc12a1 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D012964:Sodium