Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice

T. Matoba, H. Shimokawa, M. Nakashima, Y. Hirakawa, Y. Mukai, K. Hirano, H. Kanaide, A. Takeshita

研究成果: Article査読

577 被引用数 (Scopus)

抄録

The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several endothelium-derived relaxing factors, such as prostacyclin, nitric oxide (NO), and the previously unidentified endothelium-derived hyperpolarizing factor (EDHF). In this study, we examined our hypothesis that hydrogen peroxide (H2O2) derived from endothelial NO synthase (eNOS) is an EDHF. EDHF-mediated relaxation and hyperpolarization in response to acetylcholine (ACh) were markedly attenuated in small mesenteric arteries from eNOS knockout (eNOS-KO) mice. In the eNOS-KO mice, vasodilating and hyperpolarizing responses of vascular smooth muscle per se were fairly well preserved, as was the increase in intracellular calcium in endothelial cells in response to ACh. Antihypertensive treatment with hydralazine failed to improve the EDHF-mediated relaxation. Catalase, which dismutates H2O2 to form water and oxygen, inhibited EDHF-mediated relaxation and hyperpolarization, but it did not affect endothelium-independent relaxation following treatment with the K+ channel opener levcromakalim. Exogenous H2O2 elicited similar relaxation and hyperpolarization in endothelium-stripped arteries. Finally, laser confocal microscopic examination with peroxide-sensitive fluorescence dye demonstrated that the endothelium produced H2O2 upon stimulation by ACh and that the H2O2 production was markedly reduced in eNOS-KO mice. These results indicate that H2O2 is an EDHF in mouse small mesenteric arteries and that eNOS is a major source of the reactive oxygen species.

本文言語English
ページ(範囲)1521-1530
ページ数10
ジャーナルJournal of Clinical Investigation
106
12
DOI
出版ステータスPublished - 2000

ASJC Scopus subject areas

  • 医学(全般)

フィンガープリント

「Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル