title: The efficacy and tolerability of azilsartan in mice with left ventricular pressure overload or acute myocardial infarction.
abstract: Angiotensin II receptor blockers (ARBs) are used for the treatment of patients with heart failure and hypertension. Yet their safety has been questioned by some who observed delayed cardiac healing and scar thinning after myocardial infarction (MI). To clarify potential efficacy and safety of ARBs, we administered Azilsartan medoxomil, a prodrug of an ARB (Takeda Pharmaceutical Company Limited), assessed cardiac fibrosis (hydroxyproline content), left ventricular (LV) wall thickness (premortem echocardiography and caliper measurement at necropsy), and LV mass and cardiac function with high-resolution ultrasound in mice with either surgically induced LV pressure overload (aortic banding) or acute MI. Drug-treated aortic-banded mice exhibited less LV wall thickness, hypertrophy, and dilation compared with that exhibited by controls. Survival in drug-treated MI mice was greater though not significantly. Drug-treated mice with acute MI exhibited less cardiomyocyte injury reflected by LV creatine kinase content and less LV hypertrophy and dilation. Thus, Azilsartan exerted favorable biological effects on the hearts of mice subjected to LV pressure overload or MI without compromising survival consistent with its potential utility and tolerability in patients with analogous conditions.
authors: Cardiovascular Research Institute, University of Vermont College of Medicine, Colchester, VT 05446, USA.
authors: Patricia
authors: P
authors: Quinn Baumann
authors: A K M Tarikuz
authors: AK
authors: Zaman
authors: Keara
authors: K
authors: McElroy-Yaggy
authors: Burton E
authors: BE
authors: Sobel
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects; D003331:Coronary Vessels; D004452:Echocardiography; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D010069:Oxadiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D010069:Oxadiazoles; C557413:azilsartan medoxomil