V 1 /V 2 Vasopressin receptor antagonism potentiates the renoprotection of renin-angiotensin system inhibition in rats with renal mass reduction

Norberto Perico, Carla Zoja, Daniela Corna, Daniela Rottoli, Flavio Gaspari, Lloyd Haskell, Giuseppe Remuzzi

Research output: Contribution to journalArticlepeer-review

Abstract

Blockade of the renin-angiotensin system (RAS), the standard treatment for chronic proteinuric nephropathy, slows but may not halt progression of the disease, particularly when therapy is started late. Because vasopressin may also play a role in the progression of renal disease, we measured the effect of a dual V 1a and V 2 vasopressin receptor antagonist (RWJ-676070) alone or combined with angiotensin-converting enzyme inhibition or angiotensin II type 1 receptor blockade on proteinuria and renal disease progression during overt nephropathy. Twenty-one days after renal mass reduction, a time of established injury, rats were given vehicle, RWJ-676070, enalapril, losartan, RWJ-676070 plus enalapril, or losartan in drinking water for an additional 39 days. RWJ-676070 returned the blood pressure to pre-treatment levels, which were significantly lower than those in vehicle-treated rats. Enalapril, losartan, and the combined therapies reduced blood pressure to a greater extent. RWJ-676070 afforded a partial antiproteinuric effect, which was enhanced by the addition of enalapril or losartan. Renal functional impairment, and glomerular and tubular changes were partially ameliorated by RWJ-676070; parameters significantly improved with either enalapril or losartan alone and improved to a greater extent with the combined therapies. Our findings suggest that vasopressin receptor antagonists could be of additional therapeutic value in the treatment of chronic proteinuric nephropathy.

Original languageEnglish
Pages (from-to)960-967
Number of pages8
JournalKidney International
Volume76
Issue number9
DOIs
Publication statusPublished - Nov 2009

Keywords

  • ACE inhibitor
  • Angiotensin receptor blocker
  • Proteinuric nephropathy
  • Renal injury
  • Renal mass reduction
  • Vasopressin receptor antagonist

ASJC Scopus subject areas

  • Nephrology

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