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-conver ting enzyme inhibitor perindopril on diabetic glomerulopathy in rats w ith experimentally induced diabetes and explore its possible mechanism s. Methods Ninety-two adult male Wistar rats were randomly allocated i nto diabetes mellitus (DM), diabetes-mellitus + perindopril (DMP) and control (C) groups. According to the duration of diabetes or observati on (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 grou ps received perindopril 1 mg.kg(-1).d(-1), through gastric intubation. Urinary protein excretion rate was determined by the method of Coomas sie brilliant blue. Plasma renin activity, renal tissue renin activity , and plasma and renal tissue angiotensin II concentration were assaye d by radioimmunoassay (RIA). Renal tissue total RNA was extracted by t he Chomezymskis AGPC method. Renal angiotensinogen mRNA expression lev el was assessed by slot blot hybridization using a full length rat ang iotensinogen cDNA probe labelled with (32)-dCTP and a random primer. R esults There was increased activity of the renin angiotensin system in diabetic rats. Perindopril decreased proteinuria and delayed the prog ression of glomerular basement membrane thickening. However, it did no t reduce the expansion of the mesangial matrix (P<0.05). Renin activit y increased and angiotensin II concentration decreased significantly i n both plasma and renal tissue in diabetes + perindopril groups (P < 0 .05). Conclusions Perindopril may help prevent the progression of diab etic glomerulopathy, and the inhibition of renin angiotensin system ac tivity may be a mechanism for this action.