Ameliorative potential of angiotensin1-7/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 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-beta-D glucosaminadase activity, renal collagen contents, lipid profile, serum nitrite/nitrate concentration and kidney weight/body weight (%). Treatments with Ang(1-7) (576 microg/kg/day i.p. for 4 weeks) and Ang(1-7) plus A-779 (744 microg/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 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 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.
Singh
T
T
Department of Pharmacology, ISF College of Pharmacy, Moga, India.
Singh
K
K
Sharma
P L
PL
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001806:Blood Urea Nitrogen; D003094:Collagen / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology; D050171:Dyslipidemias / Q000188:drug therapy; D010446:Peptide Fragments / Q000494:pharmacology*; D011507:Proteinuria / Q000188:drug therapy; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000037:antagonists & inhibitors; D013311:Streptozocin
C092006:7-Ala-angiotensin (1-7); D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D013311:Streptozocin; D003094:Collagen; D000803:Angiotensin I; C118790:angiotensin I (1-7)