内皮素A受体拮抗剂WS009A对大鼠低氧性肺动脉高压形成的影响

The effect of ETA receptor antagonist WS009A on the pathogenesis of hypoxic pulmonary hypertension in rats]

OBJECTIVE: To investigate the effect of ETA receptor antagonist, WS009A, on the pathogenesis of hypoxic pulmonary hypertension in rats. METHODS: In the course of chronic hypoxia, rats were treated with WS009A (10 mg/kg) by a siliastic catheter inserted in the left external jugular vein. RESULTS: The measured values of mean pulmonary arterial pressure (mPAP) were 2.7 +/- 0.33, 3.97 +/- 0.47 [symbol: see text] 2.39 +/- 0.27 kPa in the control, the hypoxic and the WS009A treated groups, respectively. The percentages of vascular wall area/total vascular area (MA%) were 0.26 +/- 0.03, 0.52 +/- 0.04, 0.32 +/- 0.07, respectively. The percentages of vascular wall thickness/vascular external diameter(MT%) were 0.14 +/- 0.02, 0.31 +/- 0.03, 0.18 +/- 0.05, respectively. The ratios of right ventricular wall to left ventricle plus septum[RV/(LV + S)] were 0.24 +/- 0.02, 0.35 +/- 0.03, 0.26 +/- 0.03, respectively. The variance analysis revealed there were decreases in mPAP and the ratio of RV/(LV + S) in WS009A group (P < 0.01, compared with those in hypoxic group). There were no haemodynamic and right ventricular hypertrophy differences between WS009A group and control group. The MT% and MA% in WS009A groups were higher than those in controls, but there were significantly decreased MT% and MA% in WS009A group as compared with those in hypoxic group (P < 0.01). CONCLUSION: The ETA receptor antagonist, WS009A, attenuates the pulmonary vascular wall remodelling and the pulmonary hypertension induced by chronic hypoxia.