Contractile Actions of Endothelin-1 in Isolated Helical Strips from Rat Pulmonary Artery

Abstract

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(-8) M) 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(-11) M ET-1 potentiated the serotonin-induced contraction (10(-7)-3 x 10(-6) M), 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(-6) M), quinacrine (10(-6) M), and AA861 (10(-6) M), but not by indomethacin (10(-7) M) and baicalein (10(-6) M). 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.