[Leukotoxin, 9,10-epoxy-12-octadecenoate, causes vasodilation in isolated pulmonary artery rings preconstricted with endothelin 1].
Leukotoxin, a cytochrome P450-dependent metabolite of linoleate synthesized by neutrophils, caused dose dependent vasodilation (10(15)-5 x 10(-4) M) of isolated rat pulmonary arterial rings preconstricted with endothelin 1 (10(-8) M), although similar doses of linoleate had no effect. The relaxing effect of leukotoxin was largely ablated by mechanical denudation of the endothelium and by treatment with L-NMMA (1 mM) and methylene blue (5 x 10(-6) M), but not indomethacin (10(-5) M). Endothelium-independent relaxation of leukotoxin was not inhibited by pretreatment with nicardipine (10(-6) M) in both pulmonary arterial rings and aortic rings. In A7r5 cultured rat aortic smooth muscle cells, leukotoxin markedly inhibited Ca2+ uptake in the basal nonstimulated state, and in the stimulated state with endothelin 1. We conclude that leukotoxin causes vascular tone-dependent vasodilation via augmentation of EDRF production, and causes decrease of intracellular calcium concentration that is not related to the dihydropyridine-sensitive calcium channel, which may be a mechanism of the endothelium-independent relaxation caused by leukotoxin.
Takahashi
H
H
Third Department of Internal Medicine, Fukui Medical School, Japan.
Ishizaki
T
T
Ameshima
S
S
Kishi
Y
Y
Sasaki
F
F
Nakai
T
T
Miyabo
S
S
Ozawa
T
T
D000818:Animals; D016232:Endothelins / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008041:Linoleic Acids / Q000494:pharmacology*; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000494:pharmacology*
D016232:Endothelins; D008041:Linoleic Acids; D014665:Vasodilator Agents; C051208:9,10-epoxy-12-octadecenoic acid