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 poor prognosis and is a drug-resistant disease. Recently, it has been reported that continuous intravenous prostacyclin (PGI2) administration is effective for PH. In this study, we compared the effects of chronic treatment with an endothelin-A- (ETA) receptor antagonist with an oral PGI2 analog on PH in rats. We administered the ETA-receptor antagonist TA-0201 or beraprost sodium (BPS), which is an orally active PGI2 analog, to monocrotaline- (MCT) induced PH rats. Each drug was given orally for 19 days. The rats were divided into the following four groups: (1) normal rats with vehicle (control); (2) PH rats with vehicle treatment (PH + vehicle); (3) PH rats with TA-0201 treatment (0.5 mg/kg/day) (PH + TA-0201); (4) PH rats with BPS treatment (100 microg/kg/day) (PH + BPS). Nineteen days after MCT injection, Pp/Ps [the ratio of right ventricular (RV) systolic pressure to systemic systolic blood pressure) and the ratio of the 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 (healthy) group. The increase in Pp/Ps and RV/BW was significantly depressed in the PH + TA-0201 group and PH + BPS group to a similar extent. The expression of beta-myosin heavy chain (MHC) mRNA, a molecular marker for cardiac hypertrophy, in the RV was greatly increased in the PH + vehicle group and this increase was inhibited in the PH + TA-0201 group and PH + BPS group to a similar effect. In conclusion, treatment with an ETA-receptor antagonist or an oral PGI2 analog is comparably effective in the prevention of progression of PH and RV hypertrophy.
Ueno
M
M
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Miyauchi
T
T
Sakai
S
S
Goto
K
K
Yamaguchi
I
I
D000284:Administration, Oral; D000818:Animals; D065128:Endothelin Receptor Antagonists; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy*; D008297:Male; D016686:Monocrotaline; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D013449:Sulfonamides / Q000627:therapeutic use*
D065128:Endothelin Receptor Antagonists; D011743:Pyrimidines; D044022:Receptor, Endothelin A; D013449:Sulfonamides; C113972:T 0201; C048081:beraprost; D016686:Monocrotaline; D011464:Epoprostenol