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Cited by 722

The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.

Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice

Open access
Matoba, Tetsuya, Shimokawa, Hiroaki, Nakashima, Mikio, Hirakawa, Yoji, Mukai, Yasushi, Hirano, Katsuya, Kanaide, Hideo, Takeshita, Akira·2000·Journal of Clinical Investigation
DOI 10.1172/jci10506
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Abstract

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 (H(2)O(2)) 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 H(2)O(2) 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 H(2)O(2) elicited similar relaxation and hyperpolarization in endothelium-stripped arteries. Finally, laser confocal microscopic examination with peroxide-sensitive fluorescence dye demonstrated that the endothelium produced H(2)O(2) upon stimulation by ACh and that the H(2)O(2) production was markedly reduced in eNOS-KO mice. These results indicate that H(2)O(2) is an EDHF in mouse small mesenteric arteries and that eNOS is a major source of the reactive oxygen species.

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Metadata

Authors
Matoba, T., Shimokawa, H., Nakashima, M., Hirakawa, Y., Mukai, Y., Hirano, K., Kanaide, H., & Takeshita, A.
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2000-12-15
Volume
106
Issue
12
Pages
1521-1530
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci10506
OpenAlex
W2146056013
Cited by
722
References
40
FWCI
18.90
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. https://app.cochat.ai/papers/10.1172/jci10506
The paper
Matoba, T., Shimokawa, H., Nakashima, M., Hirakawa, Y., Mukai, Y., Hirano, K., Kanaide, H., & Takeshita, A. (2000). Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. Journal of Clinical Investigation. https://doi.org/10.1172/jci10506

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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.