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Vascular control of the CO2/H+-dependent drive to breathe.


ABSTRACT: Respiratory chemoreceptors regulate breathing in response to changes in tissue CO2/H+. Blood flow is a fundamental determinant of tissue CO2/H+, yet little is known regarding how regulation of vascular tone in chemoreceptor regions contributes to respiratory behavior. Previously, we showed in rat that CO2/H+-vasoconstriction in the retrotrapezoid nucleus (RTN) supports chemoreception by a purinergic-dependent mechanism (Hawkins et al., 2017). Here, we show in mice that CO2/H+ dilates arterioles in other chemoreceptor regions, thus demonstrating CO2/H+ vascular reactivity in the RTN is unique. We also identify P2Y2 receptors in RTN smooth muscle cells as the substrate responsible for this response. Specifically, pharmacological blockade or genetic deletion of P2Y2 from smooth muscle cells blunted the ventilatory response to CO2, and re-expression of P2Y2 receptors only in RTN smooth muscle cells fully rescued the CO2/H+ chemoreflex. These results identify P2Y2 receptors in RTN smooth muscle cells as requisite determinants of respiratory chemoreception.

SUBMITTER: Cleary CM 

PROVIDER: S-EPMC7521922 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Vascular control of the CO<sub>2</sub>/H<sup>+</sup>-dependent drive to breathe.

Cleary Colin M CM   Moreira Thiago S TS   Takakura Ana C AC   Nelson Mark T MT   Longden Thomas A TA   Mulkey Daniel K DK  

eLife 20200914


Respiratory chemoreceptors regulate breathing in response to changes in tissue CO<sub>2</sub>/H<sup>+</sup>. Blood flow is a fundamental determinant of tissue CO<sub>2</sub>/H<sup>+</sup>, yet little is known regarding how regulation of vascular tone in chemoreceptor regions contributes to respiratory behavior. Previously, we showed in rat that CO<sub>2</sub>/H<sup>+</sup>-vasoconstriction in the retrotrapezoid nucleus (RTN) supports chemoreception by a purinergic-dependent mechanism (Hawkins et  ...[more]

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