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

Author(s):Show less -

Hawkins, Virginia E. ; Takakura, Ana C. ; Trinh, Ashley ; Malheiros-Lima, Milene R. ; Cleary, Colin M. ; Wenker, Ian C. ; Dubreuil, Todd ; Rodriguez, Elliot M. ; Nelson, Mark T. ; Moreira, Thiago S. ; Mulkey, Daniel K.

• Document type: Journal article
• Source: eLIFE; v. 6, APR 7 2017.
• Web of Science Citations: 17

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 CO(2)ventilatory 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. (AU)

• FAPESP's process: 14/07698-6 - Contribution of catecholaminergic neurons of the rostral ventrolateral medulla in the respiratory control
• Grantee: Milene Rodrigues Malheiros Lima
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/22406-1 - Respiratory anatomofunctional changes observed in an experimental model of Parkinson 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
• FAPESP's process: 16/22069-0 - Amelioration of the brainstem vascular imbalances in an spontaneously hypertensive rats with exercise
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Regular Research Grants