GLUCAGON-LIKE PEPTIDE-1 RECEPTOR ACTIVATION AND ANGIOTENSIN RECEPTOR BLOCKADE DECREASE NADPH OXIDASE-4 PROTEIN EXPRESSION AND URINARY ALBUMIN EXCRETION IN A MODEL OF METABOLIC SYNDROME
Benny Escobedo1, Ruben Rodriguez1, Andrew Lee1, Meagan Moreno1, Akira Nishiyama2, Rudy Ortiz1.
1University of California, Merced, Merced, CA, 2Kagawa Medical University, Miki-cho, Kita-gun, Kagawa, JP.
Diabetic nephropathy is associated with oxidative stress and increased urinary albumin excretion. Angiotensin receptor type 1 (AT1) blockade improves renal oxidative stress via downregulation of NOX 4 and improves overall kidney damage by reducing albumin excretion. Glucagon-like peptide-1 receptor (GLP-1r) activation decreases glomerular NOX 4 expression and albumin excretion in streptozotocin-induced diabetic rats. To test the hypothesis that the combination of AT1 blockade and GLP-1r activation decreases oxidative stress and subsequent kidney damage, we measured renal NOX 4 protein expression and albumin excretion in 5 rat groups: untreated lean LETO (n = 7), untreated obese OLETF (n = 9), OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan /kg/d; n = 9), OLETF + GLP-1 mimetic (Exe; 10 ug exenatide/kg/d; n = 7), and OLETF + ARB + exenatide (combo; n = 6). Renal NOX 4 protein expression increased in OLETF compared to LETO. ARB and Exe decreased it, and combo treatment decreased it further. Albumin excretion increased in OLETF compared to LETO. ARB and Exe decreased it, and combo treatment decreased it further. These data suggest that AT1 blockade and GLP-1r activation ameliorate oxidative stress, highlighting the impact of the activation of these receptors in the pathogenesis of diabetes-associated renal impairments.