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

Abstract

Respiratory chemoreceptors regulate breathing in response to changes in tissue CO 2 /H + . Blood flow is a fundamental determinant of tissue CO 2 /H + , yet little is known regarding how regulation of vascular tone in chemoreceptor regions contributes to respiratory behavior. Previously, we showed in rat that CO 2 /H + -vasoconstriction in the retrotrapezoid nucleus (RTN) supports chemoreception by a purinergic-dependent mechanism (Hawkins et al., 2017). Here, we show in mice that CO 2 /H + dilates arterioles in other chemoreceptor regions, thus demonstrating CO 2 /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 CO 2 , and re-expression of P2Y 2 receptors only in RTN smooth muscle cells fully rescued the CO 2 /H + chemoreflex. These results identify P2Y 2 receptors in RTN smooth muscle cells as requisite determinants of respiratory chemoreception.