Summary: Endothelin-1 (ET-1) caused a concentration-dependent contraction of helical strips from rat pulmonary arteries. Removal of endothelial cells did not change the response to ET-1. ET-1 (10-8M) induced a small contraction of the arterial strips in the absence of extracellular Ca2+ (31.0% of the contraction in the presence of extracellular Ca2+ ). Pretreatment of pulmonary arterial strips with 6 x 10-11M ET-1 potentiated the serotonin-induced contraction (10-7-3 x 10-6M), but showed no significant effect on KCl-induced contraction. The ET-1-induced potentiation of the response to serotonin was prevented by nordihydroguaiaretic acid (3 x 10-6M), quinacrine (10-6M), and AA861 (10_6M), but not by in-domethacin (10-7M) and baicalein (10-6M). These results suggest that ET-1 may cause pulmonary hypertension through a direct vasoconstrictor action and potentiation of serotonin-induced contraction, which may involve the 5-lipoxygenase pathway.