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 language | English |
|---|---|
| Pages (from-to) | 960-967 |
| Number of pages | 8 |
| Journal | Kidney International |
| Volume | 76 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Nov 2009 |
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Keywords
- ACE inhibitor
- Angiotensin receptor blocker
- Proteinuric nephropathy
- Renal injury
- Renal mass reduction
- Vasopressin receptor antagonist
ASJC Scopus subject areas
- Nephrology
Cite this
V 1 /V 2 Vasopressin receptor antagonism potentiates the renoprotection of renin-angiotensin system inhibition in rats with renal mass reduction. / Perico, Norberto; Zoja, Carla; Corna, Daniela; Rottoli, Daniela; Gaspari, Flavio; Haskell, Lloyd; Remuzzi, Giuseppe.
In: Kidney International, Vol. 76, No. 9, 11.2009, p. 960-967.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - V 1 /V 2 Vasopressin receptor antagonism potentiates the renoprotection of renin-angiotensin system inhibition in rats with renal mass reduction
AU - Perico, Norberto
AU - Zoja, Carla
AU - Corna, Daniela
AU - Rottoli, Daniela
AU - Gaspari, Flavio
AU - Haskell, Lloyd
AU - Remuzzi, Giuseppe
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - ACE inhibitor
KW - Angiotensin receptor blocker
KW - Proteinuric nephropathy
KW - Renal injury
KW - Renal mass reduction
KW - Vasopressin receptor antagonist
UR - http://www.scopus.com/inward/record.url?scp=70350057331&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350057331&partnerID=8YFLogxK
U2 - 10.1038/ki.2009.267
DO - 10.1038/ki.2009.267
M3 - Article
C2 - 19625993
AN - SCOPUS:70350057331
VL - 76
SP - 960
EP - 967
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 9
ER -