Role of ET_A-receptor antagonist in protecting rats against acute pulmonary embolism

Objective To study the role of ET_A-receptor antagonist, ambrisentan in protecting rats against acute pulmonary embolism (APE). Methods Sixty SD rats were randomly divided into normal control group (n=10), model group (n=25), ambrisentan treatment group (n=25). Thirty minutes after the rats in model group received intragastric injection of 0.9% normal saline and those in ambrisentan treatment group received intragastric injection of ambrisentan (40 mg/kg), an APE model was established by injecting collagen + epinephrine via the tail vein to observe the mortality of rats. The right ventricular systolic pressure, right ventricular index and mean pulmonary artery pressure were recorded using a multichannel physiology recorder, the expression of atrial natriuretic peptide (ANP) mRNA in right ventricular muscle was detected by RT-PCR, and the difference in 3 groups was compared after the survived rats were given drugs, once a day for 1 week. Results The mortality was obviously lower in ambrisentan treatment group than in model group (P< 0.05). The right ventricular systolic pressure and mean pulmonary artery pressure were signifcantly lower in the survived rats of ambrisentan treatment group than in those of model group 1 week after drug treatment and signifcantly higher than in control group (P< 0.05). Ambrisentan inhibited the expression of ANP mRNA in myocardium (P< 0.05) and the right ventricular index was lower in Ambrisentan group than in model group (P< 0.05). Conclusion Ambrisentan, an ET_A-receptor antagonist, can decrease the mortality of APC rats, relieve their secondary pulmonary arterial hypertension and improve their right ventricular function.