Angiotensin II plays a pivotal role in the development of diabetic nephropathy, but it remains controversial as to the best approach to effectively block the actions of this hormone in the kidney. The aim of the present study was to explore the effects of long-term treatment (8 months) with a combination of an angiotensin type 1 (AT1) receptor antagonist, irbesartan (15 mg/kg per day), and an angiotensin-converting enzyme (ACE) inhibitor, captopril (100 mg/kg per day), in diabetic spontaneously hypertensive rats. Captopril treatment reduced blood pressure (163±3 mmHg versus diabetic 201±3 mmHg), but not albumin excretion rate (43.8×/÷1.3 mg/day versus diabetic 46.8×/÷1.4 mg/day). Irbesartan treatment was associated with a similar reduction in blood pressure (173±3 mmHg) to captopril, and albumin excretion rate was reduced (14×/÷1.5 mg/day). The combination of irbesartan and captopril induced further reductions in blood pressure (140±3 mmHg) and albumin excretion rates (4.0×/÷1.5 mg/day). Gene expression of transforming growth factor β-1 was reduced by all treatments to a similar level as assessed by in situ hybridization. These results demonstrate the additive hypotensive and anti-albuminuric effects of an ACE inhibitor and an AT1 receptor, suggesting that combination therapy is an approach not only more effective at reducing blood pressure, but also at retarding the development of diabetic nephropathy.
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April 25 2001
Additive hypotensive and anti-albuminuric effects of angiotensin-converting enzyme inhibition and angiotensin receptor antagonism in diabetic spontaneously hypertensive rats
Zemin CAO;
Zemin CAO
1Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg West 3081, Victoria, Australia
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Fabrice BONNET;
Fabrice BONNET
1Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg West 3081, Victoria, Australia
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Belinda DAVIS;
Belinda DAVIS
1Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg West 3081, Victoria, Australia
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Terri J. ALLEN;
Terri J. ALLEN
1Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg West 3081, Victoria, Australia
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Mark E. COOPER
Mark E. COOPER
1Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg West 3081, Victoria, Australia
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Publisher: Portland Press Ltd
Received:
October 31 2000
Revision Received:
January 22 2001
Accepted:
February 27 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2001
2001
Clin Sci (Lond) (2001) 100 (6): 591–599.
Article history
Received:
October 31 2000
Revision Received:
January 22 2001
Accepted:
February 27 2001
Citation
Zemin CAO, Fabrice BONNET, Belinda DAVIS, Terri J. ALLEN, Mark E. COOPER; Additive hypotensive and anti-albuminuric effects of angiotensin-converting enzyme inhibition and angiotensin receptor antagonism in diabetic spontaneously hypertensive rats. Clin Sci (Lond) 1 June 2001; 100 (6): 591–599. doi: https://doi.org/10.1042/cs1000591
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