Simultaneous angiotensin receptor blockade and glucagon-like peptide-1 receptor activation ameliorate albuminuria in obese insulin-resistant rats.

Simultaneous angiotensin receptor blockade and glucagon-like peptide-1 receptor activation ameliorate albuminuria in obese insulin-resistant rats. Clin Exp Pharmacol Physiol. 2019 Nov 01;: Authors: Rodriguez R, Escobedo B, Lee AY, Thorwald M, Godoy-Lugo JA, Nakano D, Nishiyama A, Parkes DG, Ortiz RM Abstract Insulin resistance increases renal oxidant production by up-regulating NADPH oxidase 4 (Nox4) expression contributing to oxidative damage and ultimately albuminuria. Inhibition of the renin-angiotensin system (RAS) and activation of glucagon-like peptide-1 (GLP-1) receptor signaling may reverse this effect. However, whether angiotensin receptor type 1 (AT1) blockade and GLP-1 receptor activation improve oxidative damage and albuminuria through different mechanisms is not known. Using insulin resistant Otsuka Long Evan Tokushima Fatty (OLETF) rats, we tested the hypothesis that simultaneous blockade of AT1 and activation of GLP-1r additively decrease oxidative damage and urinary albumin excretion (Ualb V) in the following groups: (1) untreated, lean LETO (n=7), (2) untreated, obese OLETF (n=9), (3) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan /kg/d; n=9), (4) OLETF + GLP-1 mimetic (EXE; 10 ug exenatide/kg/d; n=7), and (5) OLETF + ARB + exenatide (Combo; n=6). Mean kidney Nox4 protein expression and nitrotyrosine (NT) levels were 30% and 46% greater, respectively, in OLETF compared to LETO. Conversely, Nox4 protein e...
Source: Clinical and Experimental Pharmacology and Physiology - Category: Drugs & Pharmacology Authors: Tags: Clin Exp Pharmacol Physiol Source Type: research