[Effects of metoprolol on cardiac function and myocyte calcium regulatory protein expressions in rabbits with experimental heart failure].
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.
Zou
Cao
C
Department of Cardiology, First Affiliated Hospital of Suzhou University, Suzhou, China. nkzc75@hotmail.com
Liu
Zhi-Hua
ZH
Jiang
Bin
B
Song
Jian-Ping
JP
Jiang
Ting-Bo
TB
Yang
Xiang-Jun
XJ
Li
Hong-Xia
HX
Han
Lian-Hua
LH
Li
Bing-Yan
BY
Jiang
Wen-Ping
WP
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
D002135:Calcium-Binding Proteins; D008790:Metoprolol; D002118:Calcium