Effect of the angiotensin II receptor blocker olmesartan on the development of murine acute myocarditis caused by coxsackievirus B3.
Ang II (Angiotensin II) has been shown to play a pivotal role in the pathophysiology of various organs, especially the cardiovascular system. The effects of ARBs (Ang II receptor blockers) in the treatment of hypertension, congestive heart failure and myocardial fibrosis have been analysed extensively in human trials, as well as animal models, and the focus of interest is now directed to its pleiotropic effects, especially on inflammatory disorders. To investigate the effects of a new ARB, olmesartan, on immune-mediated myocardial injury, the protective effects of olmesartan on the development of murine acute myocarditis caused by CVB3 (coxsackievirus B3) were analysed. Olmesartan and a non-specific vasodilator hydralazine lowered systolic blood pressure of mice on day 7 after virus inoculation to a similar extent. Olmesartan significantly decreased myocardial inflammation compared with controls, whereas hydralazine significantly increased this. Olmesartan significantly decreased the expression of IFN-gamma (interferon-gamma), FasL (Fas ligand), iNOS (inducible nitric oxide synthase) and PFP (pore-forming protein) in myocardial tissue, indicating that olmesartan suppressed the activation of infiltrating killer lymphocytes. Olmesartan also decreased the expression of CVB3 genomes in myocardial tissue as well as serum levels of 8-OHdG (8-hydroxy-2'-deoxyguanosine), a biomarker of oxidative-stress-induced DNA damage. The findings suggest that olmesartan prevents myocardial damage and may improve the prognosis of patients with acute myocarditis; however, further investigations are needed before clinical use.
Seko
Yoshinori
Y
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan. sekoyosh-tky@umin.ac.jp
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000208:Acute Disease; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004353:Drug Evaluation, Preclinical; D029822:Enterovirus B, Human / Q000302:isolation & purification; D004769:Enterovirus Infections / Q000503:physiopathology / Q000517:prevention & control*; D016679:Genome, Viral; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000627:therapeutic use; D007093:Imidazoles / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000503:physiopathology / Q000517:prevention & control* / Q000821:virology; D013777:Tetrazoles / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D016207:Cytokines; D007093:Imidazoles; D018836:Inflammation Mediators; D013777:Tetrazoles; D014665:Vasodilator Agents; D006830:Hydralazine; D000080242:8-Hydroxy-2'-Deoxyguanosine; C437965:olmesartan; D003849:Deoxyguanosine