Contractile actions of endothelin-1 in isolated helical strips from rat pulmonary artery: potentiation of serotonin-induced contraction.
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.
Itoh
H
H
First Department of Internal Medicine, Faculty of Medicine, University of Mie, Japan.
Hiraoka
N
N
Higuchi
H
H
Ito
M
M
Konishi
T
T
Nakano
T
T
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013189:SRS-A / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D016232:Endothelins; D013189:SRS-A; D016718:Arachidonic Acid; D012701:Serotonin; D011189:Potassium Chloride; D002118:Calcium