Original ArticleThe Efficacy and Tolerability of Azilsartan in Obese Insulin-Resistant Mice with Left Ventricular Pressure OverloadTarikuz Zaman, A.K.M. MBBS; McLean, Danielle L. PhD; Sobel, Burton E. MDAuthor Information Cardiovascular Research Institute and Department of Medicine, University of Vermont College of Medicine, Colchester, VT. Reprints: A.K.M. Tarikuz Zaman, MBBS, Department of Medicine, University of Vermont College of Medicine, Colchester Research Facility, 208 South Park Drive, Colchester, VT 05446 (e-mail: email@example.com). This research was funded by a grant from Takeda Pharmaceuticals USA, Inc. Received April 19, 2013 Accepted June 04, 2013 Journal of Cardiovascular Pharmacology: October 2013 - Volume 62 - Issue 4 - p 381-387 doi: 10.1097/FJC.0b013e31829f0c1b Buy Metrics Abstract Abstract: Angiotensin II receptor blockers (ARBs) are used widely for the treatment of heart failure. However, their use in obese and insulin-resistant patients remains controversial. To clarify their potential efficacy in these conditions, we administered azilsartan medoxomil (azilsartan), a prodrug of an angiotensin II receptor blocker to mice fed a high-fat diet (HFD) with left ventricular (LV) pressure overload (aortic banding). LV fibrosis (hydroxyproline), cardiac plasminogen activator inhibitor-1 (PAI-1; a marker of profibrosis), and creatine kinase (a marker of myocardial viability and energetics) were assessed. LV wall thickness and cardiac function were assessed echocardiographically. Mice given a HFD were obese and insulin resistant. Their LV hypertrophy was accompanied by greater LV PAI-1 and reduced LV creatine kinase compared with normal diet controls. Drug treatment reduced LV wall thickness, hypertrophy, and PAI-1 and increased cardiac output after aortic banding compared with results in HFD vehicle controls. Thus, azilsartan exerted favorable biological effects on the hearts of obese insulin-resistant mice subjected to LV pressure overload consistent with its potential utility in patients with analogous conditions. © 2013 by Lippincott Williams & Wilkins.