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

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Author(s):
Cleary, Colin M. ; Moreira, Thiago S. ; Takakura, Ana C. ; Nelson, Mark T. ; Longden, Thomas A. ; Mulkey, Daniel K.
Total Authors: 6
Document type: Journal article
Source: eLIFE; v. 9, p. 23-pg., 2020-09-14.
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 P2Y(2) receptors in RTN smooth muscle cells as the substrate responsible for this response. Specifically, pharmacological blockade or genetic deletion of P2Y(2) from smooth muscle cells blunted the ventilatory response to CO2, and re-expression of P2Y(2) receptors only in RTN smooth muscle cells fully rescued the CO2/H+ chemoreflex. These results identify P2Y(2) receptors in RTN smooth muscle cells as requisite determinants of respiratory chemoreception. (AU)

FAPESP's process: 16/23281-3 - Encephalic regions responsible for neuroplasticity observed in respiratory response induced by hypercapnia in a modelo of Parkinson's Disease
Grantee:Ana Carolina Takakura Moreira
Support Opportunities: Regular Research Grants
FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
Grantee:Thiago dos Santos Moreira
Support Opportunities: Research Projects - Thematic Grants