Zacopride attenuates pressure overload-induced ventricular remodeling in rats / 中国病理生理杂志

ABSTRACT

AIM:To investigate the protective effect of zacopride (ZAC) on the pressure-overload left ventricular remodeling in the rats induced by coarctation of abdominal aorta.METHODS:Male Sprague-Dawley (SD) rats with pressure overload were induced by the coarctation of abdominal aorta.The model rats were intraperitoneally administered with ZAC, chloroquine (Chlor) , and zacopride+chlorquine (ZAC+Chlor).The study duration was 8 weeks.The cardiac structure and function were assessed by echocardiography.The heart weight/body weight (HW/BW) ratio and the left ventricular weight/body weight (LVW/BW) ratio were calculated.The changes of structure and shape in myocardial tissue were observed with HE staining.The ultrastructure of the myocytes was observed under transmission electron microscope.The inward rectifier potassium channel (IK1) protein expression was determined by Western blot.The mRNA expression of Kir2.1 was detected by RT-PCR.RESULTS:Compared with vehicle group, ZAC improved cardiac function, as indicated by the decreased left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic dimension (LVESD) (P<0.05) , and the increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01).The HW/BW and LVW/BW ratios were significantly decreased, and the cross-sectional area of the cardiomyocytes was significantly less in ZAC group than that in vehicle group (P<0.01).The ultrastructure of the myocytes was significantly improved.Chlor blocked the protective effect of zacopride on the pressure-overload left ventricular remodeling.The protein level ofmRNA expression of Kir2.1 in the cardiac tissues in ZAC group were significantly increased compared with vehicle group (P<0.01).CONCLUSION:ZAC significantly attenuates pressure overload-induced ventricular remodeling in rats.