Effects of imidapril and captopril on streptozotocin-induced diabetic nephropathy in mice

We investigated whether the prevention of the development of diabetic nephr opathy by angiotensin-converting enzyme inhibitors is associated with decre ases in renal angiotensin-converting enzyme activity and/or blood pressure in diabetic mice. C57B1/6 mice were injected with streptozotocin (300 mg/kg , i.v.) and randomized to receive either imidapril (1 and 5 mg/kg) or capto pril (10 and 50 mg/kg) or vehicle by gavage for 28 days. Each assay was per formed on 8-10 mice from each treatment. At 28 days after the start of drug treatment, imidapril and captopril significantly reduced blood pressure of the diabetic mice, and this effect of captopril was stronger than that of imidapril. On the other hand, inhibition of renal angiotensin-converting en zyme activity by imidapril was stronger than that by captopril. Imidapril a nd captopril dose-dependently inhibited urinary albumin excretion to simila r extents, but they failed to inhibit the renal hypertrophy and elevation o f creatinine clearance. Total renal angiotensin-converting enzyme activity was significantly reduced in diabetic mice, but immunohistochemical localiz ation of angiotensin-converting enzyme was intensive in the vasculature and glomeruli of the diabetic kidney. In conclusion, both effects on blood pre ssure and angiotensin-converting enzyme activity may be involved in the pre vention of development of diabetic nephropathy by imidapril and captopril i n streptozotocin-induced diabetic mice. The data suggest that the degrees o f contribution of their effects on blood pressure and renal angiotensin-con verting enzyme activity to the inhibition of urinary albumin excretion may be different between the two angiotensin-converting enzyme inhibitors. (C) 2000 Elsevier Science B.V. All rights reserved.