title: [The effects of combined beta(1) adrenergic receptor antagonist and beta(2) adrenergic receptor agonist therapy on cardiac function and myocardial apoptosis in heart failure rats].
abstract: OBJECTIVE
  To observe the effects of combined beta(1) adrenergic receptor (AR) antagonist with beta(2)AR agonist therapy on cardiac function and cardiomyocyte apoptosis in heart failure rats.
  
  
  METHODS
  Heart failure was induced by isoproterenol and rats were randomly divided into metoprolol group (50 mg/kg twice daily/gavage, n = 11), combined treatment group (fenoterol 125 microg/kg and metoprolol 50 mg/kg twice daily/gavage, n = 11) and placebo group (saline, n = 10), another normal 9 male Wistar rats served as control group. After 8 weeks' treatment, cardiac function, apoptosis index (AI), Caspase-3 activity, expression levels of bcl-2 and bax protein, organ weight/body weight and collagen volume fraction (CVF) were evaluated.
  
  
  RESULTS
  (1) Left ventricular end diastolic dimension, left ventricular end systolic dimension and E/A ratio were significantly increased and fractional shortening, ejection fraction significantly reduced post isoproterenol (all P < 0.05 vs. control) and these changes were significantly attenuated by metoprolol alone (all P < 0.05 vs. placebo) and further attenuated by the metoprolol and fenoterol combination therapy (all P < 0.05 vs. placebo and metoprolol). (2) Left ventricular weight to body weight ratio, lung weight to body weight ratio and CVF were also significantly reduced in metoprolol and combined treatment group than those in placebo group (all P < 0.01). (3) Compared with placebo group, AI and Caspase-3 activity were significantly lower in metoprolol group (all P < 0.01 vs. placebo) and further reduced in combined treatment group (all P < 0.01 vs. metoprolol). (4) The expression level of bax protein was significantly lower in metoprolol group while bcl-2/bax significantly higher than those in placebo group. These changes were more significant in combined treatment group (all P < 0.01 vs. metoprolol).
  
  
  CONCLUSIONS
  beta(1)AR antagonist in combination with beta(2)AR agonist further improved the cardiac function and prevented cardiac remodeling compared with using beta(1)AR antagonist alone in heart failure rats. Downregulated bax and upregulated bcl-2/bax expressions might contribute to the observed beneficial therapy effects by reducing cardiomyocyte apoptosis in these animals.
authors.affiliation: Department of Cardiology, First Clinical Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Wei-min
authors.initials: WM
authors.lastname: Li
authors.forename: Run-tao
authors.initials: RT
authors.lastname: Gan
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.forename: Jing-xia
authors.initials: JX
authors.lastname: Shen
authors.forename: Chun-hong
authors.initials: CH
authors.lastname: Xiu
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004359:Drug Therapy, Combination; D006333:Heart Failure / Q000188:drug therapy*; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists