Protective effect of the angiotensin-converting enzyme inhibitor perindopril on diabetic glomerulopathy in streptozotocin-induced diabetic rats.

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Protective effect of the angiotensin-converting enzyme inhibitor perindopril on diabetic glomerulopathy in streptozotocin-induced diabetic rats

OBJECTIVES: To evaluate the protective effect of the angiotensin-converting enzyme inhibitor perindopril on diabetic glomerulopathy in rats with experimentally induced diabetes and explore its possible mechanisms. METHODS: Ninety-two adult male Wistar rats were randomly allocated into diabetes mellitus (DM), diabetes mellitus + perindopril (DMP) and control (C) groups. According to the duration of diabetes or observation (1, 3, 6 months), each group was randomly subdivided into DM1, DM3, DM6; DMP1, DMP3, DMP6; and C1, C3, C6 groups. Diabetes was induced by intraperitoneal injection of streptozotocin. The rats in the DMP groups received perindopril 1 mg.kg-1.d-1, through gastric intubation. Urinary protein excretion rate was determined by the method of Coomassie brilliant blue. Plasma renin activity, renal tissue renin activity, and plasma and renal tissue angiotensin II concentration were assayed by radioimmunoassay (RIA). Renal tissue total RNA was extracted by the Chomezymskis AGPC method. Renal angiotensinogen mRNA expression level was assessed by slot blot hybridization using a full length rat angiotensinogen cDNA probe labelled with 32P-dCTP and a random primer. RESULTS: There was increased activity of the renin angiotensin system in diabetic rats. Perindopril decreased proteinuria and delayed the progression of glomerular basement membrane thickening. However, it did not reduce the expansion of the mesangial matrix (P < 0.05). Renin activity increased and angiotensin II concentration decreased significantly in both plasma and renal tissue in diabetes + perindopril groups (P < 0.05). CONCLUSIONS: Perindopril may help prevent the progression of diabetic glomerulopathy, and the inhibition of renin angiotensin system activity may be a mechanism for this action.