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Methods and Findings
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Methods Find Exp Clin Pharmacol 2010, 32(1): 19
ISSN 0379-0355
Copyright 2010 Clarivate Analytics
CCC: 0379-0355
DOI: 10.1358/mf.2010.32.1.1434160
Ameliorative potential of angiotensin1-7/Mas receptor axis in streptozotocin-induced diabetic nephropathy in rats
Kamal, K., Teji, T., Manjeet, M., Pyre, P.
The present study was designed to investigate the effects of angiotensin1-7 (Ang1-7) a Mas receptor agonist, and A-779, a Mas receptor antagonist, in streptozotocin-induced diabetic nephropathy (DN). 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 DN was assessed biochemically and morphologically by measuring serum creatinine, creatinine clearance, blood urea nitrogen (BUN), proteinuria, urinary N-acetyl-β-D glucosaminadase activity, renal collagen contents, lipid profile, serum nitrite/nitrate concentration and kidney weight/body weight (%). Treatments with Ang1-7 (576 µg/kg/day i.p. for 4 weeks) and Ang1-7 plus A-779 (744 µg/kg/day i.p. for 4 weeks) were started after 4 weeks of STZ administration. The treatment with Ang1-7 attenuated STZ-induced nephropathy in rats 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 Ang1-7 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 Ang1-7 treatment. It may be concluded that activation by specific agonists of the Mas receptor may be useful in combating glomerular damage in DN.

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