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.
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.
Nielsen
Birgitte
B
Medical Research Laboratories (Diabetes and Endocrinology), Institute of Experimental Clinical Research, Aarhus UniversitY Hospital, Aarhus, Denmark. Birgitte.Nielsen@dadlnet.dk
Grønbaek
Henning
H
Osterby
Ruth
R
Flyvbjerg
Allan
A
D000419:Albuminuria / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D007668:Kidney / Q000473:pathology; D009568:Nitrendipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004656:Enalapril; D009568:Nitrendipine