Angiotensin-converting enzyme inhibitor improves force and Ca2 +--frequency relationships in myocytes from rats with heart failure.
OBJECTIVE
The objectives were to study the effects of an ACE inhibitor on the force-frequency relationship (FFR) and its possible mechanism in isolated failing myocytes.


RESULTS
Male Wistar rats were randomized into a heart failure group treated with perindopril (CHF-T, 3 mg.kg(-1)d-1), a heart failure group without treatment (CHF-C) and a sham-operated group (PS). Heart failure was induced by constriction of the abdominal aorta. All groups were further followed up for 12 weeks. Left ventricular myocytes were isolated. Cell-shortening fraction (FS) and intracellular calcium transients were measured at different frequency field stimulations. A negative force-frequency relationship (FFR) was found in the CHF-C group compared with the positive-negative biphasic FFR in the PS group, and a flat FFR in the CHF-T group. Intracellular Ca2+ frequency relationships (CaFRs) were positive-negative biphasic in both the PS and CHF-T groups, whereas a negative CaFR was found in the CHF-C group. Regardless of the stimulation frequency, FS significantly correlated with [Ca2+]imax in the PS or CHF-C groups. Compared to the PS group, protein levels of SERCA2 significantly decreased and NCX1 increased in the CHF-C group. In the CHF-T group, these changes were reduced.


CONCLUSIONS
The ACE inhibitor could improve the impaired FFR of isolated failing myocytes. This effect was possibly mediated via ameliorating the disturbance of CaFR.
Liao
Xinxue
X
Department of Cardiology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
He
Jiangui
J
Ma
Hong
H
Tao
Jun
J
Chen
Wenfang
W
Leng
Xiuyu
X
Mai
Weiyi
W
Zhen
Wutao
W
Liu
Jun
J
Wang
Lichun
L
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000814:Aniline Compounds; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D018613:Microscopy, Confocal; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D020913:Perindopril / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000187:drug effects / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000378:metabolism*; D014966:Xanthenes
D000806:Angiotensin-Converting Enzyme Inhibitors; D000814:Aniline Compounds; D002135:Calcium-Binding Proteins; D005456:Fluorescent Dyes; D019831:Sodium-Calcium Exchanger; D014966:Xanthenes; C059715:Fluo-3; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D020913:Perindopril