Effects of ACE inhibitor on the calcium transient and calcium handling proteins in ventricular myocytes from rats with heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transient and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.</p><p><b>METHODS</b>Male Wistar rats were randomized to heart failure group treated with perindopril (CHF-T, 3 mg.kg(-1).d(-1)), heart failure group without treatment (CHF-C) and sham-operated group (PS) after heart failure was induced by constricting abdominal aorta for 16 weeks. All groups were further followed up for 12 weeks. Left ventricular myocytes were isolated, and single cell shortening fraction and [Ca(2+)](i) were simultaneously measured through laser scanning confocal microscope under the field stimulation (1.0 Hz). RT-PCR and Western blot were performed to evaluate the level of mRNA and protein of Na(+)-Ca(2+) exchanger (NCX(1)), sarcoplasmic Ca(2+)-ATPase (SERCA(2)) and phospholamban (PLB).</p><p><b>RESULTS</b>The fraction of cell shortening (FS%) and [Ca(2+)](i max) (nmol/L) were significantly smaller in group CHF-C than group PS (FS%: 7.51 +/- 1.15 vs 13.21 +/- 1.49; [Ca(2+)](i max): 330.85 +/- 50.05 vs 498.16 +/- 14.07; both P < 0.01). And in CHF-T group, FS and [Ca(2+)](i max) were greater than those in CHF-C group. In CHF-C group, the left ventricular mRNA of NCX(1) and PLB were significantly higher than those in PS group (R(NCX)(1)/beta-Actin: 0.51 +/- 0.12 vs 0.19 +/- 0.06, P < 0.01; R(PLB)/beta-Actin: 0.26 +/- 0.12 vs 0.20 +/- 0.08, P = 0.045), yet SERCA(2) mRNA was lower than PS group (0.48 +/- 0.10 vs 0.80 +/- 0.11, P < 0.01). In CHF-T group, the mRNA levels of NCX(1) and SERCA(2) were just in the midst of the CHF-C and PS group, and had statistical significance respectively (all P < 0.05). In CHF - C and CHF - T group, the protein levels of NCX(1) were 1.141 +/- 0.047 and 1.074 +/- 0.081 times PS group, respectively (both P < 0.05), and SERCA(2) protein levels were respectively 0.803 +/- 0.100 and 0.893 +/- 0.084 times as high as in PS group (both P < 0.05). The protein expression of NCX(1) and SERCA(2) were also different between CHF-C and CHF-T groups (both P < 0.05).</p><p><b>CONCLUSION</b>ACE inhibitor could improve cardiac function in CHF through directly enhancing the contractility of single myocardial cell, and these effects were probably mediated by its role in preventing the deleterious changes of calcium transient and calcium handling proteins in CHF.</p>

Effect of angiotensin converting enzyme inhibitor on the calcium transients and calcium handling proteins in ventricular myocytes from rats with heart failure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic heart failure (CHF) is associated with calcium transients and calcium handling proteins. Angiotensin converting enzyme (ACE) inhibitor has been demonstrated to have beneficial effect on CHF. Yet studies addressed to the relationship between ACE inhibitor and calcium transients in CHF are rare. The aim of this study was to investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transients and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.</p><p><b>METHODS</b>Male Wistar rats were randomized to heart failure group treated with perindopril [CHF-T, 3 mg.kg(-1).d(-1)], heart failure group without treatment (CHF-C) and sham-operated group (PS). Heart failure was induced by abdominal aortic constriction. All groups were further followed up for 12 weeks. Left ventricular myocytes were then isolated. Single cell shortening fraction and [Ca(2+)]i were simultaneously measured by laser scanning confocal microscope under the field stimulation (1.0 Hz). Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot were performed to evaluate the changes of mRNA and protein of Na(+)-Ca(2+) exchanger (NCX1), sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) and phospholamban (PLB).</p><p><b>RESULTS</b>The fraction of cell shortening (FS%) and [Ca(2+)]imax (nmol/L) were significantly reduced in group CHF-C compared with group PS (FS%: 7.51 +/- 1.15 vs 13.21 +/- 1.49; [Ca(2+)]i max: 330.85 +/- 50.05 vs 498.16 +/- 14.07; both P < 0.01), and restored at least partially in CHF-T group. In CHF-C group, the left ventricular mRNA of NCX1 and PLB were significantly upregulated in comparing with PS group (RNCX1/beta-Actin: 0.51 +/- 0.12 vs 0.19 +/- 0.06, P < 0.01; RPLB/beta-Actin: 0.26 +/- 0.12 vs 0.20 +/- 0.08, P < 0.05), while SERCA2 mRNA was downregulated (0.48 +/- 0.10 vs 0.80 +/- 0.11, P < 0.01). The mRNA levels of NCX1 and SERCA2 in CHF-T group were between the CHF-C and PS group, and the differences of the latter two groups were significant (all P < 0.05). In CHF-C and CHF-T groups, the protein expression of NCX1 were 1.141 +/- 0.047 and 1.074 +/- 0.081 times of that in PS group respectively (both P < 0.05), and SERCA2 protein levels were 0.803 +/- 0.100 and 0.893 +/- 0.084 times of that in PS group respectively (both P < 0.05). The protein expression of NCX1 and SERCA2 in the CHF-C and CHF-T groups is significantly different (both P < 0.05).</p><p><b>CONCLUSION</b>ACE inhibitor could improve cardiac function of failing heart through directly enhancing the contractility of single cardiomyocyte, and these effects are probably mediated by its roles in preventing the deleterious changes of calcium transients and calcium handling proteins in CHF.</p>