Renal enlargement and insulin-like growth factor-1 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 glomerular hyperfiltration. Possible mechanisms for these changes could be the direct effects of growth factors such as insulin-like growth factor-1 and angiotensin II. We investigated whether treatment with trandolapril, an angiotensin converting enzyme inhibitor, prevented renal enlargement in streptozotocin-diabetic rats. Seven groups of male Wistar rats were studied: C (control + placebo); CL (control + low-dose trandolapril, 0.01 mg.kg-1.day-1); CH (control + high-dose trandolapril, 0.5 mg.kg-1.day-1; DP (diabetic + placebo); DI (diabetic, insulin-treated); DL (diabetic + low-dose trandolapril); DH (diabetic + high-dose trandolapril) and DI (diabetic + insulin). From day 2 glucose 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, showed marked hyperglycaemia throughout the study. Kidney weight was greater in the diabetic, non insulin-treated groups compared with the control and insulin-treated groups. After 24 h of diabetes, kidney insulin-like growth factor-1 content was significantly increased from baseline levels in groups DP, DL and DH but by 48 h these levels had returned to normal. Renal tissue angiotensin converting enzyme activity was similar in groups C and DI but significantly reduced in all trandolapril-treated animals. Despite inhibiting renal angiotensin converting enzyme activity renal enlargement with increased tissue insulin-like growth 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 diabetes. Renal accumulation of insulin-like growth factor-1 appears to be an important factor in early renal hypertrophy and its effects are not modulated by angiotensin converting enzyme or angiotensin II.
New
J P
JP
Department of Medicine, University of Newcastle upon Tyne, UK.
Canavan
J P
JP
Flyvbjerg
A
A
Hamon
G
G
Bilous
R W
RW
Marshall
S M
SM
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology*; D007328:Insulin / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D007211:Indoles; D007328:Insulin; C052035:trandolapril; D007334:Insulin-Like Growth Factor I; D007703:Peptidyl-Dipeptidase A; D012083:Renin