Purinergic regulation of vascular tone in the retrotrapezoid nucleus is specialized to support the drive to breathe.

Abstract

Cerebral blood flow is highly sensitive to changes in CO₂/H⁺ where an increase in CO₂/H⁺ causes vasodilation and increased blood flow. Tissue CO₂/H⁺ also functions as the main stimulus for breathing by activating chemosensitive neurons that control respiratory output. Considering that CO₂/H⁺-induced vasodilation would accelerate removal of CO₂/H⁺ and potentially counteract the drive to breathe, we hypothesize that chemosensitive brain regions have adapted a means of preventing vascular CO₂/H⁺-reactivity. Here, we show in rat that purinergic signaling, possibly through P2Y_2/4 receptors, in the retrotrapezoid nucleus (RTN) maintains arteriole tone during high CO₂/H⁺ and disruption of this mechanism decreases the CO₂ventilatory response. Our discovery that CO₂/H⁺-dependent regulation of vascular tone in the RTN is the opposite to the rest of the cerebral vascular tree is novel and fundamentally important for understanding how regulation of vascular tone is tailored to support neural function and behavior, in this case the drive to breathe.