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Archives of Toxicology

, Volume 80, Issue 5, pp 280–285 | Cite as

Inhibition of endothelial nitric oxide synthase activity and suppression of endothelium-dependent vasorelaxation by 1,2-naphthoquinone, a component of diesel exhaust particles

  • Yang Sun
  • Keiko Taguchi
  • Daigo Sumi
  • Shigeru Yamano
  • Yoshito Kumagai
Organ Toxicity and Mechanisms

Abstract

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 on 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 μM, 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 μM) 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.

Keywords

1,2-Naphthoquinone Nitric oxide Endothelial nitric oxide synthase Vasorelaxation Diesel exhaust particles 

Abbreviations

1,2-NQ

1,2-Naphthoquinone

1,2-DDN

trans-1,2-Dihydroxy-1,2-dihydronaphthalene

NO

Nitric oxide

eNOS

Endothelial nitric oxide synthase

Ach

Acetylcholine

SNP

Sodium nitroprusside

Notes

Acknowledgments

We are especially grateful to Ms. F. Miyamasu for grammatical corrections in the preparation of this manuscript. This research was supported in part by Grant-in-Aid #15390184 and #15659141 (YK) for scientific research from the Ministry of Education, Science, Culture and Sports of Japan.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Yang Sun
    • 1
  • Keiko Taguchi
    • 1
  • Daigo Sumi
    • 1
  • Shigeru Yamano
    • 2
  • Yoshito Kumagai
    • 1
    • 3
  1. 1.Department of Environmental Medicine, Doctoral Programs in Medical Sciences, Graduate School of Comprehensive SciencesUniversity of TsukubaIbarakiJapan
  2. 2.Faculty of Pharmaceutical Sciences Fukuoka UniversityFukuokaJapan
  3. 3.Southern California Particle Center and SupersiteLos AngelesUSA

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