Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice

Kimiko Yamamoto, Takaaki Sokabe, Takahiro Matsumoto, Kimihiro Yoshimura, Masahiro Shibata, Norihiko Ohura, Toru Fukuda, Takashi Sato, Keisuke Sekine, Shigeaki Kato, Masashi Isshiki, Toshiro Fujita, Mikio Kobayashi, Koichi Kawamura, Hirotake Masuda, Akira Kamiya, Joji Ando

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Abstract

The structure and function of blood vessels adapt to environmental changes such as physical development and exercise1-3. This phenomenon is based on the ability of the endothelial cells to sense and respond to blood flow4-6; however, the underlying mechanisms remain unclear. Here we show that the ATP-gated P2X4 ion channel7,8, expressed on endothelial cells and encoded by P2rx4 in mice, has a key role in the response of endothelial cells to changes in blood flow. P2rx4-/- mice do not have normal endothelial cell responses to flow, such as influx of Ca2+ and subsequent production of the potent vasodilator nitric oxide (NO). Additionally, vessel dilation induced by acute increases in blood flow is markedly suppressed in P2rx4-/- mice. Furthermore, P2rx4 -/- mice have higher blood pressure and excrete smaller amounts of NO products in their urine than do wild-type mice. Moreover, no adaptive vascular remodeling, that is, a decrease in vessel size in response to a chronic decrease in blood flow, was observed in P2rx4-/- mice. Thus, endothelial P2X4 channels are crucial to flow-sensitive mechanisms that regulate blood pressure and vascular remodeling.

Original languageEnglish
Pages (from-to)133-137
Number of pages5
JournalNature Medicine
Volume12
Issue number1
DOIs
Publication statusPublished - 2006 Jan 1

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Yamamoto, K., Sokabe, T., Matsumoto, T., Yoshimura, K., Shibata, M., Ohura, N., Fukuda, T., Sato, T., Sekine, K., Kato, S., Isshiki, M., Fujita, T., Kobayashi, M., Kawamura, K., Masuda, H., Kamiya, A., & Ando, J. (2006). Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. Nature Medicine, 12(1), 133-137. https://doi.org/10.1038/nm1338