Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in human mesenteric arteries

Tetsuya Matoba, Hiroaki Shimokawa, Hiroshi Kubota, Keiko Morikawa, Takako Fujiki, Ikuko Kunihiro, Yasushi Mukai, Yoji Hirakawa, Akira Takeshita

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235 Citations (Scopus)

Abstract

The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several vasodilating factors, including prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor (EDHF). We have recently identified that endothelium-derived hydrogen peroxide (H2O2) is an EDHF in mice. The present study was designed to examine whether this is also the case in humans. Bradykinin elicited endothelium-dependent relaxations and hyperpolarizations in the presence of indomethacin and Nω-nitro-L-arginine, which thus were attributed to EDHF, in human mesenteric arteries. The EDHF-mediated relaxations were significantly inhibited by catalase, an enzyme that specifically decomposes H2O2, whereas catalase did not affect endothelium-independent hyperpolarizations to levcromakalim. Exogenous H2O2 elicited relaxations and hyperpolarizations in endothelium-stripped arteries. Gap junction inhibitor 18α-glycyrrhetinic acid partially inhibited, whereas inhibitors of cytochrome P450 did not affect the EDHF-mediated relaxations. These results indicate that H2O2 is also a primary EDHF in human mesenteric arteries with some contribution of gap junctions.

Original languageEnglish
Pages (from-to)909-913
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume290
Issue number3
DOIs
Publication statusPublished - Jan 1 2002

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Matoba, T., Shimokawa, H., Kubota, H., Morikawa, K., Fujiki, T., Kunihiro, I., Mukai, Y., Hirakawa, Y., & Takeshita, A. (2002). Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in human mesenteric arteries. Biochemical and Biophysical Research Communications, 290(3), 909-913. https://doi.org/10.1006/bbrc.2001.6278