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

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(2)S formed by cystathionine ?-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(2)S that mediate 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.

SUBMITTER: Morikawa T 

PROVIDER: S-EPMC3268316 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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

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

Proceedings of the National Academy of Sciences of the United States of America 20120109 4

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(2)S formed by cystathionine β-synthase (CBS) and CO ge  ...[more]