title: [Effects of metoprolol on cardiac function and myocyte calcium regulatory protein expressions in rabbits with experimental heart failure].
abstract: OBJECTIVE
  To investigate the effects of metoprolol on cardiac function and myocyte calcium regulatory protein expressions in rabbits with heart failure.
  
  
  METHODS
  Rabbit heart failure model was established by aortic insufficiency induced volume overload followed 14 days later by pressure overload induced by abdominal aorta constricting (HF, n = 11), another 8 rabbits with heart failure were treated with metoprolol (ME) for 6 weeks, sham-operated rabbits (n = 11) served as control. Cardiac function was measured by echocardiography at the end of study. Caffeine-induced calcium transients of myocytes loaded by Fluo-3/AM were observed under Laser scanning confocal microscope. Calcium regulatory protein expression was determined by Western blot analysis.
  
  
  RESULTS
  Compared to control animals, the ejection fractions [EF, (45.7 +/- 3.0)% vs. (72. 6 +/- 5.0)%, P < 0.01] and the amplitude of caffeine-induced calcium transients [(16.0 +/- 3.5) FI vs. (43.5 +/- 6.2) FI, P < 0.01] were significantly decreased while its time to peak was significantly prolonged [(129.8 +/- 14.5) s vs. (52.2 +/- 7.4) s, P < 0.01] in HF rabbits. The RyR2 (0.106 +/- 0.007 vs. 0.203 +/- 0.021, P < 0.01) and the ratio of SERCA2a and NCX (1.22 +/- 0.23 vs. 1.96 +/- 0.12, P < 0.01) were also significantly reduced in myocytes of HF rabbits. Metoprolol significantly attenuated the decrease of EF [(60.2 +/- 5.1)%], the amplitude of calcium transient [(32.8 +/- 5.4) FI], the RyR2 expression (0.164 +/- 0.016) and the ratio of SERCA2a and NCX (1.68 +/- 0.17, all P < 0.05 vs. HF rabbits) and attenuated the increase of the time to peak of caffeine-induced calcium transients [(91.4 +/- 10.9) s, P < 0.05 vs. HF rabbits].
  
  
  CONCLUSIONS
  Metoprolol could improve the cardiac function possibly by preventing the alterations of calcium regulatory proteins and increasing calcium transients in failing heart.
authors: Department of Cardiology, First Affiliated Hospital of Suzhou University, Suzhou, China. nkzc75@hotmail.com
authors: Cao
authors: C
authors: Zou
authors: Zhi-Hua
authors: ZH
authors: Liu
authors: Bin
authors: B
authors: Jiang
authors: Jian-Ping
authors: JP
authors: Song
authors: Ting-Bo
authors: TB
authors: Jiang
authors: Xiang-Jun
authors: XJ
authors: Yang
authors: Hong-Xia
authors: HX
authors: Li
authors: Lian-Hua
authors: LH
authors: Han
authors: Bing-Yan
authors: BY
authors: Li
authors: Wen-Ping
authors: WP
authors: Jiang
mesh_terms: D000818:Animals; D001022:Aortic Valve Insufficiency / Q000188:drug therapy / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D008790:Metoprolol / Q000494:pharmacology* / Q000627:therapeutic use; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D011817:Rabbits
chemical_list: D002135:Calcium-Binding Proteins; D008790:Metoprolol; D002118:Calcium