Effects of ezetimibe and simvastatin on transient outward potassium current in ischemia-reperfused ventricular myocytes in rats / 天津医药

ABSTRACT

Objective To observe the impact of alone or combined use of ezetimibe and simvastatin on transient outward potassium current (Ito) in ventricular myocytes of rat model of ischemia and reperfusion (IR). Methods Seventy-five male SD rats were randomly divided into five groups, control group (CON), control-IR group (CIR), ezetimibe treatment group (EIR), simvastatin treatment group (SIR) and combined ezetimibe and simvastatin treatment group (ESIR). After two weeks of treat?ment with intragastic normal saline or drugs (ezetimibe or simvastatin), myocytes were isolated from right ventricular with colla?genaseⅡ, and Ito was recorded by whole-cell patch clamp technique. Results (1) The Ito current density at+60 mV was sig?nificantly decreased in CIR group than that of CON group (P0.05). The Ito current densities were higher in SIR group and ESIR group compared to those of CIR group. There was no significant difference in Ito current density between SIR group and ESIR group (P>0.05). (2) There was a significant increase in the half-inactivation (V1/2) in CIR group than that of CON group, but no significant differ?ence between EIR group and CIR group (P >0.05). There was a significant difference in the half-inactivation (V1/2) in SIR group and ESIR group compared to that of CIR group (P0.05). There was no significant difference in the slope factor (K) between five groups (P>0.05). (3) The time-con?stant (τ) of Ito recovery curves from inactivation was significantly higher in CIR group than that of CON group (P0.05). There was a significant difference in the time-con?stant (τ) of Ito recovery curves from inactivation in SIR group and ESIR group compared to that of CIR group (P0.05). Conclusion Simvastatin pre-treatment or ezetimibe+simvastatin pre-treatment can reverse the effect of IR on Ito of ventricular myocytes, but ezetimibe shows no such effects.