Endothelin-A-receptor antagonist and oral prostacyclin analog are comparably effective in ameliorating pulmonary hypertension and right ventricular hypertrophy in rats

Pulmonary hypertension (PH) has a Door prognosis and is a drug-resistant di sease. Recently. it has been reported that continuous intravenous prostacyc lin (PGI(2)) administration is effective for PH. In this study, we compared the effects of chronic treatment with an endothelin-A- (ETA) receptor anta gonist with an oral PGI(2) analog on PH in rats. We administered the ETA-re ceptor antagonist TA-0201 or beraprost sodium (BPS), which is an orally act ive PGI(2) analog, to monocrotaline- (MCT) induced PII rats. Each drug was given orally for 19 days. The rats were divided into the following four gro ups: (1) normal rats with vehicle (control); (2) PH rats with vehicle treat ment (PH + vehicle); (3) PH rats with TA-0201 treatment (0.5 mg/kg/day) (PN + TA-0201); (4) PH rats with BPS treatment (100 mug/kg/day) (PH + BPS). Ni neteen days after MCT injection, Pp/Ps (the ratio of right ventricular (RV) systolic pressure to systemic systolic blood pressure) and the ratio of th e RV weight to the body weight (RV/BW), indicators of PH and RV hypertrophy , were markedly higher in the PH + vehicle group than in the control (healt hy) group. The increase in Pp/Ps and RV/BW was significantly depressed in t he PH + TA-0201 group and PH + BPS group to a similar extent. The expressio n of P-myosin heavy chain (MHC) mRNA, a molecular marker for cardiac hypert rophy, in the RV was greatly increased in the PH + vehicle group and this i ncrease was inhibited in the PH + TA-0201 group and PH + BPS group to a sim ilar effect. In conclusion, treatment with an ETA-receptor antagonist or an oral PGI(2) analog is comparably effective in the prevention of progressio n of PH and RV hypertrophy.