Leukotoxin, 9,10-epoxy-12-octadecenoate, causes pulmonary vasodilation by stimulation of vascular eNOS and iNOS.
We have previously reported that leukotoxin, 9,10-epoxy-12-octadecenoate (Lx) dilates rat pulmonary arteries by means of nitric oxide synthase (NOS) activation. In this study, we investigated if Lx stimulates constitutive and/or inducible NOS. We studied the effect of the NOS inhibitors, N(G)-monomethyl-L-arginine and aminoguanidine, as well as endothelium denudation on Lx-induced rat pulmonary arterial dilation and that of aminoguanidine on Lx-induced endothelium denuded lipopolysaccharide (LPS)-treated rat pulmonary arterial dilation and tissue cGMP content. Furthermore, we assessed the effect of aminoguanidine, an inducible NOS (iNOS) inhibitor, on the cGMP content increase induced by Lx in LPS-treated human pulmonary artery smooth muscle cells (HPASMC). The NOS inhibitors and endothelium denudation significantly attenuated Lx-induced vasodilation. Aminoguanidine also significantly attenuated Lx-induced vasodilation in LPS-treated rat denuded pulmonary arteries, and attenuated Lx-induced cGMP content increase in denuded pulmonary arterial rings from LPS-treated rats and in LPS-treated HPASMC. These results suggest that Lx causes pulmonary vasodilation by stimulation of vascular endothelial NOS (eNOS) and iNOS.
Nakanishi
M
M
Third Department of Internal Medicine, Fukui Medical University, Fukui, Japan.
Ishizaki
T
T
Demura
Y
Y
Okamura
S
S
Ameshima
S
S
Sasaki
F
F
Matsukawa
S
S
Miyamori
I
I
D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005098:Exotoxins / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D008041:Linoleic Acids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005098:Exotoxins; D006146:Guanidines; D008041:Linoleic Acids; D008070:Lipopolysaccharides; C018579:leukotoxin; D019323:omega-N-Methylarginine; C051208:9,10-epoxy-12-octadecenoic acid; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D006152:Cyclic GMP; C004479:pimagedine