Effect of combination therapy with a calcium channel blocker and an angiotensin-converting enzyme inhibitor on renal hypertrophy and urinary albumin excretion in diabetic rats

Exp Diabesity Res. 2003 Jul-Sep;4(3):191-9. doi: 10.1155/EDR.2003.191.

Abstract

The objective of this study was to compare the effect of an angiotensin-converting enzyme (ACE) inhibitor and a calcium channel blocker on the development of renal changes in diabetic rats. Diabetes was induced by an intravenous injection of streptozotocin in normotensive Wistar rats. Treatment was commenced immediately in 1 set of rats with 4 treatment arms: nitrendipine (250 mg/kg fodder), enalapril (35 mg/L drinking water), both treatments in combination, or placebo. Treatment was continued for 9 weeks. Another set of rats was left with untreated diabetes for 3 months followed by 7 weeks treatment as above. When starting treatment right after induction of diabetes, nitrendipine significantly reduced urinary albumin excretion (UAE) to the nondiabetic level (P < .05) without reducing blood pressure (BP), whereas enalapril failed to significantly reduce UAE despite a reduction in BP. Combining the two treatments showed no further reduction in UAE compared to monotherapy with nitrendipine, despite a lower BP. When leaving diabetic rats untreated for 3 months, only the coadministration of nitrendipine and enalapril showed a significant reduction in UAE compared to monotherapy and placebo treatment, but showed no significant effect on BP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / drug therapy
  • Albuminuria / metabolism
  • Albuminuria / pathology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • Drug Therapy, Combination
  • Enalapril / pharmacology*
  • Female
  • Kidney / pathology
  • Nitrendipine / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Calcium Channel Blockers
  • Enalapril
  • Nitrendipine