Calcium-dependent diuretic system in preascitic liver cirrhosis.
OBJECTIVE
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.


OBJECTIVE
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.


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, PGE(2) urinary excretion, and free-water clearance in cirrhotic rats (all p<0.01 v. untreated cirrhotic animals).


CONCLUSIONS
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.
Sansoè
G
G
Division of Gastroenterology, Gradenigo Hospital, Torino, Italy. giovannisan@iol.it
Aragno
M
M
Tomasinelli
C E
CE
di Bonzo
L Valfrè
LV
Wong
F
F
Parola
M
M
D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000502:physiology*; D015232:Dinoprostone / Q000652:urine; D004231:Diuresis; D007668:Kidney / Q000503:physiopathology*; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing / Q000032:analysis / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000032:analysis / Q000502:physiology; D064466:Solute Carrier Family 12, Member 1
D010455:Peptides; D044169:Receptors, Calcium-Sensing; C578716:Slc12a1 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; C015462:polyarginine; D012964:Sodium; D015232:Dinoprostone; D002118:Calcium