Effects of endothelin receptor A antagonist FR139317 on rats with congestive heart failure

Aim: To study the effects of a selective endothelin receptor A (ETA) antago nist FR139317 on rats with congestive heart failure. Methods: A congestive heart failure model was established via left coronary artery ligation in ad ult male Wistar rats. The rats with congestive heart failure were treated w ith FR139317 at two doses (1 and 5 mg/kg(-1).d(-1) respectively for 6 weeks ) or with vehicle. Hemodynamics, plasma level of endothelin-1 (ET-1), and m ortality rate of rats were measured. Results: Both groups treated with FR13 9317 (high and low dose) have lower mortality rate (25.0% and 28.6% vs 50.0 %) and lower plasma level of ET-1 than that of vehicle [(3.6 +/-1.2) ng/L a nd (4.9 +/-1.5) ng/L vs (5.8 +/-1.3) ng/L]. Comparing to vehicle group, lef t ventricular end-diastolic pressures of the FR139317-treated groups were i mproved significantly [(12 +/-6) mmHg and (14 +/-7) mmHg vs (22 +/-9) mmHg] . FR139317 at a higher dose reduced the mean arterial pressure of the rats with congestive heart failure and decreased the plasma concentration of end othelin to a closer level of rats with normal heart function than lower dos e. Conclusion: Selective ETA antagonist FR139317 improved the hemodynamics and reduced the plasma ET-1 level and the mortality of rats with congestive heart failure.