Hypotensive Effect of Endothelin-1 via Endothelin-B-Receptor Pathway on Pulmonary Circulation is Enhanced in Rats with Pulmonary Hypertension

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Abstract
Summary: 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.

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