Effect of ETA receptor antagonist BQ-123 on cardiac function and endothelin system after coronary microembolization in rats

Objective To evaluate the effects of BQ-123 on cardiac function and ventricular remodelling after coronary microembolization (CME) in rats. Methods We created a rat model of CME by injecting a suspension of autogenic microthrombotic particles into left ventricle. Three days after the procedure, the 30 surviving rats were randomly divided into 3 groups, each consisted of 10 rats: sham-operation group(SO), CME model group(CM) and BQ-123 intervention group(BQ). Rats in the BQ group received BQ-123 (400μg/kg per day, intraperitoneally) for 4 weeks. Plasma and myocardial endothelin-1 (ET-1) were measured by radioimmunoassay. And serial echocardiography was performed to monitor alterations of left ventricular end-systolic and end-diastolic diameter (LVESD, LVEED), and left ventricular short-axis fraction shortening(LVFS) and ejection fraction (LVEF), and physiologicography to document the changes of left ventricular systolic pressure (LVSP) and end-diastolic pressure pressure(LVEDP), and left ventricular maximum positive and negative dp/dt (±LVdp/dtmax). Results Compared with sham-operated group, both LVEDD and LVESD were increased (P【0.01), whereas LVFS and LVEF were significantly decreased (P【0.01) in CME group; LVEDP was markedly increased, while LVSP and±LVdp/ dtmax markedly reduced in CME group (P【0.01); plasma and tissue ET-1 levels increased in CME group (P【0.01). BQ-123 intervention significantly decreased both the plasma and tissue ET-1 levels (P【0.01), and markedly increased LVFS and LVEF, with significant improvement of LVSP and±LVdp/ dtmax (P【0.01). Conclusions Treatment with BQ-123 prevents ventricular remodeling after CME due to suppression of the endothelin system.