Angiotensin-converting enzyme inhibitor improves force and Ca2 +--frequency relationships in myocytes from rats with heart failure.

OBJECTIVES

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.

METHODS AND 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.

CONCLUSION

The ACE inhibitor could improve the impaired FFR of isolated failing myocytes. This effect was possibly mediated via ameliorating the disturbance of CaFR.