AMELIORATIVE POTENTIAL OF ANGIOTENSIN(1-7)/MAS RECEPTOR AXIS IN STREPTOZOTOCIN-INDUCED DIABETIC NEPHROPATHY IN RATS

The present study was designed to investigate the effects of angiotensin(1-7)(Ang(1-7)) a Mas receptor agonist, and A-779, a Mac receptor antagonist, in streptozotocin-induced diabetic nephropathy (ON). A single administration of streptozotocin (STZ) (50 mg/kg i.p.) to rats produced diabetes, and diabetic nephropathy developed after 8 weeks of STZ administration. The extent of ON was assessed biochemically and morphologically by measuring serum creatinine, creatinine clearance, blood urea nitrogen (BUN), proteinuria, urinary N-acetyl-beta-D glucosaminadase activity, renal collagen contents, lipid profile, serum nitrite/nitrate concentration and kidney weight/body weight (%). Treatments with Ang(1-7) (576 mu g/kg/day i.p. for 4 weeks) and Ang(1-7) plus A-779 (744 mu g/kg/day i.p. for 4 weeks) were started after 4 weeks of STZ administration. The treatment with Ang(1-7) attenuated STZ-induced nephropathy in rots by decreasing proteinuria, renal collagen content and by improving endothelial functions without preventing tubular damage. it has been shown for the first time that treatment with Ang(1-7) decreases dyslipidemia and BUN in diabetic rats, implying a renoprotective effect of the peptide. However; serum creatinine, creatinine clearance and kidney weight/body weight (%) remained unaffected with Ang(1-7) treatment. it may be concluded that activation by specific agonists of the Mas receptor may be useful in combating glomerular damage in DN.