title: Angiotensin II type 1 receptor blocker, valsartan, prevented cardiac fibrosis in rat cardiomyopathy after autoimmune myocarditis.
abstract: Favorable effects of angiotensin II type 1 receptor blockers on patients with ischemic or idiopathic dilated cardiomyopathy have already been suggested by several human trials but their effects on inflammatory cardiomyopathy remain unknown. We investigated the effects of the angiotensin II type 1 receptor blocker, valsartan, in chronic heart failure after inflammatory cardiomyopathy. Autoimmune myocarditis was induced in Lewis rats by injection with porcine cardiac myosin. In the phase of chronic heart failure, from day 28 until day 70, rats were treated by oral administration of valsartan. Three groups were designated: 1 ml saline, 10 mg/kg valsartan, and 30 mg/kg valsartan. On the 73rd day, hemodynamic parameters, pathological findings and the expression levels of r-ANP mRNA of the ventricle were examined, and were compared with the saline control. The ventricular weight/body weight ratio and area of fibrosis was decreased in the 30 mg/kg valsartan group. The left ventricular end-diastolic pressure and the central venous pressure were decreased in a dose-dependent manner in both valsartan groups, while the first pressure derivatives +dP/dt and -dP/dt did not differ among the three groups. A high dose of valsartan reduced the expression of tissue ANP mRNA compared with the saline group. In conclusion,valsartan suppressed myocardial hypertrophy and fibrosis, and it improved the hemodynamics and cardiac function in an animal model of post-myocarditis dilated cardiomyopathy.
authors.affiliation: First Department of Internal Medicine, Niigata University Graduate School of Medicine, Niigata, Japan. tachihh@med.niigata-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tachikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Liu
authors.initials: L
authors.lastname: Hui
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Manabu
authors.initials: M
authors.lastname: Hayashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Abe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kashimura
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kato
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000503:physiopathology; D009202:Cardiomyopathies / Q000188:drug therapy / Q000503:physiopathology; D004719:Endomyocardial Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D009205:Myocarditis / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D000068756:Valsartan; D016276:Ventricular Function
chemical_list: D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine