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1 Department of Pharmacology, the Panum Institute, University of Copenhagen, Copenhagen, Denmark
2 University Institute of Pathology, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark
* To whom correspondence should be addressed. E-mail: fitj{at}farmakol.ku.dk.
We have previously shown that systemic treatment with the somatostatin analogue octreotide have marked beneficial effects on renal function in rats with liver cirrhosis induced by common bile duct ligation (CBL). In the present study we tested the hypothesis that octreotide has direct effect on renal tubular function. Rats (CBL or Sham-CBL) were intrarenally treated with low dose octreotide in a long acting release formulation, which had no systemic actions (100 µg/kg b.w. as a single dose). Rats receiving sc low dose octreotide were used as controls. The rats were chronically instrumented and renal function was examined four weeks after CBL or sham-operation. Intrarenal octreotide administration (IROA) prevented sodium retention in CBL rats without changes in renal plasma flow, GFR or circulating levels of aldosterone and vasopressin. Renal clearance studies revealed that IROA normalized the increased natriuretic efficacy of furosemide found in CBL rats. Furthermore, IROA protected against the development of hypertrophy of the inner stripe of the outer medulla and thereby the increased volume of thick ascending limb of Henles loop (TAL) epithelium found in CBL rats. Finally western blot analyses on outer medullary homogenates showed increased abundance of the furosemide sensitive NKCC2 co-transporter in CBL rats. IROA did not affect the abundance of NCKK2 within the outer medulla. Together with the histological findings these results indicate that IROA reduce the total number of NKCC2 within the outer medulla. In conclusion the results indicate a direct intrarenal effect of octreotide on TAL function and morphology in cirrhotic rats.
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