Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway

Takayuki Morikawa, Mayumi Kajimura, Tomomi Nakamura, Takako Hishiki, Tsuyoshi Nakanishi, Yoshinori Yukutake, Yoshiko Nagahata, Mami Ishikawa, Katsuji Hattori, Toshiki Takenouchi, Takao Takahashi, Isao Ishii, Kazuko Matsubara, Yasuaki Kabe, Shinichiro Uchiyama, Eiichiro Nagata, Moataz M. Gadalla, Solomon H. Snyder, Makoto Suematsu

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Enhancement of cerebral blood flow by hypoxia is critical for brain function, but signaling systems underlying its regulation have been unclear. We report a pathway mediating hypoxia-induced cerebral vasodilation in studies monitoring vascular disposition in cerebellar slices and in intact mouse brains using two-photon intravital laser scanning microscopy. In this cascade, hypoxia elicits cerebral vasodilation via the coordinate actions of H 2S formed by cystathionine β-synthase (CBS) and CO generated by heme oxygenase (HO)-2. Hypoxia diminishes CO generation by HO-2, an oxygen sensor. The constitutive CO physiologically inhibits CBS, and hypoxia leads to increased levels of H 2S thatmediate the vasodilation of precapillary arterioles. Mice with targeted deletion of HO-2 or CBS display impaired vascular responses to hypoxia. Thus, in intact adult brain cerebral cortex of HO-2-null mice, imaging mass spectrometry reveals an impaired ability to maintain ATP levels on hypoxia.

Original languageEnglish
Pages (from-to)1293-1298
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number4
DOIs
Publication statusPublished - 2012 Jan 24

Keywords

  • Energy metabolism
  • Gas biology
  • Gasotransmitter
  • Neurovascular unit

ASJC Scopus subject areas

  • General

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