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Astrocyte mitochondria produce nitric oxide from nitrite to modulate cerebral blood flow during brain hypoxia

Isabel N. ChristieiD, Shefeeq M. TheparambiliD, Maxim DoroniniD, Patrick Steven HosfordiD, Alexey BrazheiD, Adrian J. HobbsiD, Alexey V. SemyanoviD, Andrey Y. AbramoviD, Plamena R. AngelovaiD, Alexander V. GourineiD

Abstract

In low oxygen conditions, increases in cerebral blood flow maintain brain oxygen delivery but the mechanisms underlying hypoxia-induced dilations of cerebral vasculature are incompletely understood. Here we show that astrocytes accumulate nitrite and in response to hypoxia produce nitric oxide via mitochondrial reduction of nitrite by a molybdenum-containing enzyme sulfite oxidase. These data suggest that astrocytes can modulate cerebral blood flow in accord with brain tissue oxygenation via mitochondrial production of nitric oxide.

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