title: Betaxolol improves the survival rate and changes natriuretic peptide expression in rats with heart failure.
abstract: The cardioprotective effects of betaxolol were studied in a rat model with heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization, Lewis rats were divided into four groups; 0.1 mg/kg betaxolol per day (group 0.1), 1.0 mg/kg betaxolol per day (group 1), 10 mg/kg betaxolol per day (group 10), and vehicle (0.5% methylcellulose, group V) (all groups, n = 13). After oral administration for 1 month, the heart weight, the mRNA expression of atrial natriuretic peptide and brain natriuretic peptide in the left ventricle, the plasma atrial natriuretic peptide concentration, the mean blood pressure, the heart rate, the central venous pressure, the peak left ventricular pressure, the left ventricular end-diastolic pressure and its first derivative +/-dP/dt, and the area of myocardial fibrosis were measured. Betaxolol reduced the heart rate, the levels of atrial natriuretic peptide and brain natriuretic peptide mRNA expression and the atrial natriuretic peptide concentration [group N (normal rats), 367 +/- 4 beats/min, 100%, 100% and 78 +/- 7 pg/ml, respectively; group V, 391 +/- 9 beats/min, 761 +/- 68% versus group N, 317 +/- 42% versus group N and 4374 +/- 312 pg/ml, respectively; group 0.1, 387 +/- 10 beats/min, 621 +/- 78%, 288 +/- 41% and 2875 +/- 331 pg/ml, respectively; group 1, 323 +/- 9 beats/min, 442 +/- 84%, 148 +/- 12% and 884 +/- 51 pg/ml, respectively; and group 10, 312 +/- 8 beats/min, 97 +/- 18%, 92 + 9% and 453 +/- 53 pg/ml, respectively], and increased survival (group V, 62%; group 0.1, 69%; groups N, 1 and 10, 100%). Betaxolol did not significantly alter the heart weight, the hemodynamic parameters or the area of fibrosis. These observations suggest that betaxolol may improve the survival rate by reducing sudden death and changing the atrial natriuretic peptide and brain natriuretic peptide mRNA expression in patients with heart failure.
authors.affiliation: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan. watanabe@niigata-pharm.ac.jp
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Wen
authors.initials: W
authors.lastname: Juan
authors.forename: Gurusamy
authors.initials: G
authors.lastname: Narasimman
authors.forename: Meilei
authors.initials: M
authors.lastname: Ma
authors.forename: Mikio
authors.initials: M
authors.lastname: Inoue
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Mir I I
authors.initials: MI
authors.lastname: Wahed
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Go
authors.initials: G
authors.lastname: Hasegawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tachikawa
authors.forename: Naohito
authors.initials: N
authors.lastname: Tanabe
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis*; D015784:Betaxolol / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D013552:Swine
chemical_list: D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D015784:Betaxolol