Beneficial effects of bisoprolol on the survival of hypertensive diastolic heart failure model rats.
BACKGROUND
beta-blocker therapy is an established therapeutic strategy for systolic heart failure. However, its benefits in diastolic heart failure (DHF) are controversial.


OBJECTIVE
This study was designed to investigate the effects of bisoprolol on DHF.


RESULTS
Dahl salt-sensitive rats fed on 8% NaCl diet from age 6 weeks, DHF model rats, were divided into three groups at age 13 weeks. One group was treated with bisoprolol 12.5 mg/kg/day (Low dose group, n=18), one group was treated with bisoprolol 250 mg/kg/day (High dose group, n=18), and there was also an untreated group (Untreated group, n=18). The survival rate was best in the High dose group. Left ventricular hypertrophy and the expression of proinflammatory cytokines in the myocardium were significantly attenuated in the High dose group, but not in the Low dose group, and oxidative stress was most suppressed in the High dose group. Measurement with electron spin resonance revealed that bisoprolol had a potent scavenging ability, and bisoprolol attenuated the down-regulation of peroxisome proliferation-activated receptor coactivator-1alpha, an important element in the mitochondrial reactive oxygen species detoxification system.


CONCLUSIONS
beta-blocker administration, particularly at high dose, improved the survival rate of the DHF model, at least partly through the attenuation of inflammatory changes and oxidative stress.
Nishio
Mayu
M
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Sakata
Yasushi
Y
Mano
Toshiaki
T
Ohtani
Tomohito
T
Takeda
Yasuharu
Y
Miwa
Takeshi
T
Hori
Masatsugu
M
Masuyama
Tohru
T
Kondo
Takashi
T
Yamamoto
Kazuhiro
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017298:Bisoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D054144:Heart Failure, Diastolic / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006973:Hypertension / Q000150:complications*; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D020303:Rats, Inbred Dahl; D016019:Survival Analysis
D000319:Adrenergic beta-Antagonists; D017298:Bisoprolol