Nephrol Dial Transplant (2001) 16: 1343-1349
© 2001 European Renal Association-European Dialysis and Transplant Association
Renoprotective and anti-hypertensive effects of combined valsartan and perindopril in progressive diabetic nephropathy in the transgenic (mRen-2)27 rat
1 Department of Physiology, The University of Melbourne, 2 Department of Medicine, Austin & Repatriation Medical Centre, West Heidelberg, Victoria and 3 Department of Medicine, St Vincent's Hospital, Victoria, Australia
Background. We have previously reported that severe glomerulosclerosis progressively develops in the streptozotocin (STZ) diabetic transgenic (mRen-2)27 rat. In this diabetic model, monotherapy with either angiotensin converting enzyme inhibition (ACEI) or angiotensin type 1 (AT1) receptor blockade is largely renoprotective. The objective of the present study was to determine if a combination therapy at lower doses than monotherapy would confer greater renoprotection.
Methods. At 6 weeks of age, non-diabetic control and STZ diabetic female heterozygous Ren-2 rats were randomized to receive vehicle, the AT1 receptor blocker valsartan (V, 20 mg/kg/day), the ACEI perindopril (P, 6 mg/kg/day), or a combination of low-dose V+P (V, 3 mg/kg/day plus P, 0.5 mg/kg/day) for 12 weeks.
Results. Systolic blood pressure was lowered with all treatments, but the greatest reductions were observed with V monotherapy and combination V+P therapy. All treatments reduced albuminuria, the decline in glomerular filtration rate, and cortical collagen staining, to the same extent. The glomerulosclerotic index was increased with diabetes and reduced with V and P monotherapy. However, the low-dose combination therapy was more effective than single therapy and reduced severe glomerulosclerosis to levels observed in non-diabetic controls.
Conclusions. Monotherapy with either V or P reduced blood pressure and retarded the decline in renal function and glomerulosclerosis in the diabetic Ren-2 rat. Combination therapy has the additional benefit of requiring only low doses of AT1 receptor blockade and ACEI to achieve superior renoprotective effects in this diabetic nephropathy model.
Keywords: angiotensin; diabetes; glomerulosclerosis; hypertension; (mRen-2)27 rat; renin
Correspondence and offprint requests to: Dr Jennifer L. Wilkinson-Berka, Department of Physiology, The University of Melbourne, Grattan St, Parkville, Victoria 3010, Australia.
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