RENAL ENLARGEMENT AND INSULIN-LIKE GROWTH-FACTOR-I ACCUMULATION IN THE WISTAR RAT MODEL OF EXPERIMENTAL DIABETES IS NOT PREVENTED BY ANGIOTENSIN-CONVERTING ENZYME-INHIBITION

Experimental diabetes is associated with renal enlargement and glomeru lar hyperfiltration, Possible mechanisms for these changes could be th e direct effects of growth factors such as insulin-like growth factor- 1 and angiotensin II, We investigated whether treatment with trandolap ril, an angiotensin converting enzyme inhibitor, prevented renal enlar gement in streptozotocin-diabetic rats. Seven groups of male Wistar ra ts were studied: C (control + placebo); CL (control + low-dose trandol april, 0.01 mg . kg(-1). day(-1)); CH (control + high-dose trandolapri l, 0.5 mg . kg(-1). day(-1)); DP (diabetic + placebo); DI (diabetic, i nsulin-treated); DL (diabetic + low-dose trandolapril); DH (diabetic high-dose trandolapril) and DI (diabetic + insulin). From day 2 gluco se concentrations and body weight were similar in the non-diabetic and diabetic animals treated with insulin. Diabetic animals treated with placebo and low-dose trandolapril weighed significantly less compared to the control group. The diabetic groups, not treated with insulin, s howed marked hyperglycaemia throughout the study. Kidney weight was gr eater in the diabetic, non insulin-treated groups compared with the co ntrol and insulin-treated groups. After 24 h of diabetes, kidney insul in-like growth factor-1 content was significantly increased from basel ine levels in groups DP, DL and DH but by 48 h these levels had return ed to normal. Renal tissue angiotensin converting enzyme activity was similar in groups C and DI but significantly reduced in all trandolapr il-treated animals. Despite inhibiting renal angiotensin converting en zyme activity renal enlargement with increased tissue insulin-like gro wth factor-1 still occurred. This suggests that neither angiotensin II nor glomerular hyperfiltration, with raised intraglomerular pressure, play a role in the initial renal enlargement seen in experimental dia betes. Renal accumulation of insulin-like growth factor-1 appears to b e an important factor in early renal hypertrophy and its effects are n ot modulated by angiotensin converting enzyme or angiotensin II.