Inhibition of endothelial nitric oxide synthase activity and suppression of endothelium-dependent vasorelaxation by 1,2-naphthoquinone, a component of diesel exhaust particles.
Diesel exhaust particles contain redox-active quinones, such as 9,10-phenanthraquinone (9,10-PQ) and 1,2-naphthoquinone (1,2-NQ), which act as potent electron acceptors, thereby altering electron transfer tgljoint @/Set Line Joint Styleon proteins. We have previously found that 9,10-PQ inhibits constitutive nitric oxide synthase (NOS) activity, by shunting electrons away from NADPH on the cytochrome P450 reductase domain of NOS, and thus suppresses acetylcholine (Ach)-induced vasorelaxation in the aortic ring. However, the effect of 1,2-NQ on endothelial NOS (eNOS) activity is still poorly understood. With the membrane fraction of cultured bovine aortic endothelial cells, we found that 1,2-NQ was a potent inhibitor of eNOS with an IC50 value of 1.4 microM, whereas trans-1,2-dihydroxy-1,2-dihydronaphthalene (1,2-DDN), a redox-negative naphthalene analog of 1,2-NQ, did not show such an inhibitory action. Although 1,2-DDN (5 microM) did not affect Ach-mediated vasorelaxation, 1,2-NQ caused a significant suppression of Ach-induced endothelium-dependent vasorelaxation in the aortic ring. However, 1,2-NQ did not affect sodium nitroprusside-induced endothelium-independent vasorelaxation. These results suggest that 1,2-NQ is an environmental quinone that inhibits eNOS activity, thereby disrupting NO-dependent vascular tone.
Sun
Yang
Y
Department of Environmental Medicine, Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Taguchi
Keiko
K
Sumi
Daigo
D
Yamano
Shigeru
S
Kumagai
Yoshito
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D004730:Endothelium, Vascular / Q000166:cytology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009285:Naphthoquinones / Q000633:toxicity*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010084:Oxidation-Reduction; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*; D001335:Vehicle Emissions
D009285:Naphthoquinones; D001335:Vehicle Emissions; C040756:1,2-naphthoquinone; D052250:Nitric Oxide Synthase Type III