The pharmacological characterization of endothelin-1 (ET-1) in the pulmonary circulation in pulmonary hypertension (PH) is not known precisely. We investigated the effect of intravenous injection of ET-1 (1000 pmol/kg) on right ventricular systolic pressure (RVSP) (which is equal to systolic pulmonary arterial pressure) in rats with monocrotaline-induced PH. ET-1 decreased RVSP in PH rats; however, ET-1 did not alter RVSP in control rats, suggesting that ET-1 causes dilatation of the pulmonary artery in PH rats. Under pretreatment with the endothelin-A- (ETA) receptor antagonist BMS 193884, ET-1 decreased RVSP in PH rats more than in control rats, suggesting that pulmonary vasodilator action of ET-1 mediated via the ETB-receptor pathway is augmented in PH rats. Under pretreatment with the ETA/B-receptor antagonist SB 209670, the effect of ET-1 in lowering pulmonary arterial pressure was abolished in both groups of rats. These results suggest that the hypotensive effect of ET-1 on pulmonary circulation mediated via the ETB-receptor pathway is enhanced in PH rats compared with control normal rats. It is considered that the blockade of only the ETA-receptor pathway is preferable to the blockade of both the ETA- and ETB-receptor pathways in the treatment of PH.
*Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, ‡Department of Pharmacology, Institute of Basic Medical Sciences, and †Center for TARA (Tsukuba Advanced Research Alliance), University of Tsukuba, Tsukuba, Ibaraki, Japan
Address correspondence and reprint requests to Satoshi Sakai, Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan. E-mail: [email protected]
© 2000 Lippincott Williams & Wilkins, Inc.