Role of Angiotensin-(1-7) on Renal Hypertrophy in Streptozotocin-Induced Diabetes Mellitus

Abstract

Participation of angiotensin II in chronic kidney diseases including diabetic nephropathy (DN) has been extensively described. Similarly, several studies support a protective role for angiotensin-(1-7). However, other studies suggest that some of the cellular effects of angiotensin-(1-7) may be deleterious. The objective of this study was to determine the role of exogenous angiotensin-(1-7) on renal hypertrophy development in rats with streptozotocin-induced diabetes. A control group and three groups of rats with streptozotocin-induced diabetes: untreated diabetic rats, diabetic rats treated with captopril, and diabetic rats treated with angiotensin-(1-7), were studied. After two weeks of treatment, the kidneys were removed under anesthesia with pentobarbital. The kidneys were weighed and the renal cortex was separated for analysis of AT 1 R, TGF-β 1 , MASR, and ACE2 expression by western blot. Rats in the three groups with diabetes had hyperglycemia, increased food and water consumption, and higher urinary volume than control rats. Treatment with captopril or angiotensin-(1-7) reversed streptozotocin-induced renal hypertrophy, measured by kidney weight, protein/DNA ratio in renal cortex, glomerular area, or proximal tubular cells area, proteinuria, and creatinine clearance reduction. AT 1 R, TGF-β 1 , and MAS receptor expression in renal cortex of diabetic rats increased significantly as compared to controls (p < 0.05); treatment with captopril or angiotensin-(1-7) reversed such increments. ACE2 in the renal cortex decreased in diabetic rats, but it was increased after treatment with captopril or angiotensin-(1-7). These findings suggest that exogenous administration of angiotensin-(1-7) may be renoprotective in early stages of diabetes mellitus.