Renoprotective and anti-hypertensive effects of combined valsartan and perindopril in progressive diabetic nephropathy in the transgenic (mRen-2)27 rat

Nephrol Dial Transplant. 2001 Jul;16(7):1343-9. doi: 10.1093/ndt/16.7.1343.

Abstract

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 (AT(1)) 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 AT(1) 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 AT(1) receptor blockade and ACEI to achieve superior renoprotective effects in this diabetic nephropathy model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Animals, Genetically Modified
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / physiopathology*
  • Diabetic Nephropathies / prevention & control
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Heterozygote
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / physiopathology
  • Perindopril / therapeutic use*
  • Rats
  • Renin / genetics*
  • Tetrazoles / therapeutic use*
  • Valine / analogs & derivatives
  • Valine / therapeutic use*
  • Valsartan

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Tetrazoles
  • Valsartan
  • Renin
  • Valine
  • Perindopril