Watanabe Kenichi, Juan Wen, Narasimman Gurusamy, Ma Meilei, Inoue Mikio, Saito Yuki, Wahed Mir I I, Nakazawa Mikio, Hasegawa Go, Naito Makoto, Tachikawa Hitoshi, Tanabe Naohito, Kodama Makoto, Aizawa Yoshifusa, Yamamoto Tadashi, Yamaguchi Kenichi, Takahashi Toshihiro
Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
J Cardiovasc Pharmacol. 2003 Jan;41 Suppl 1:S99-103.
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.
在自身免疫性心肌炎诱导的心力衰竭大鼠模型中研究了倍他洛尔的心脏保护作用。免疫后28天，将Lewis大鼠分为四组；每天给予0.1mg/kg倍他洛尔（0.1组）、每天给予1.0mg/kg倍他洛尔（1组）、每天给予10mg/kg倍他洛尔（10组）和赋形剂（0.5%甲基纤维素，V组）（所有组，n = 13）。口服给药1个月后，测量心脏重量、左心室中心房钠尿肽和脑钠尿肽的mRNA表达、血浆心房钠尿肽浓度、平均血压、心率、中心静脉压、左心室压力峰值、左心室舒张末期压力及其一阶导数±dP/dt以及心肌纤维化面积。倍他洛尔降低了心率、心房钠尿肽和脑钠尿肽mRNA表达水平以及心房钠尿肽浓度[正常大鼠组（N组）分别为367±4次/分钟、100%、100%和78±7pg/ml；V组分别为391±9次/分钟、相对于N组为761±68%、相对于N组为317±42%和4374±312pg/ml；0.1组分别为387±10次/分钟、621±78%、288±41%和2875±331pg/ml；1组分别为323±9次/分钟、442±84%、148±12%和884±51pg/ml；10组分别为312±8次/分钟、97±18%、92±9%和453±53pg/ml]，并提高了生存率（V组为62%；0.1组为69%；N组、1组和10组为100%）。倍他洛尔未显著改变心脏重量、血流动力学参数或纤维化面积。这些观察结果表明，倍他洛尔可能通过降低猝死率和改变心力衰竭患者心房钠尿肽和脑钠尿肽mRNA表达来提高生存率。
