Purinergic regulation of vascular tone in the retrotrapezoid nucleus is specialized to support the drive to breathe
- University of Connecticut, United States
- University of São Paulo, Brazil
- College of Medicine, University of Vermont, United States
- Cited 15
- Views 1,493
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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 P2Y2/4 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.
Article and author information
Author details
Virginia E Hawkins
Funding
National Institutes of Health (HL104101)
- Daniel K Mulkey
National Institutes of Health (DK053832)
- Mark T Nelson
National Institutes of Health (HL131181)
- Mark T Nelson
Sao Paulo Research Foundation (2016/22069-0)
- Thiago S Moreira
Sao Paulo Research Foundation (2015/23376-1)
- Thiago S Moreira
Sao Paulo Research Foundation (2014/07698-6)
- Milene R Malheiros-Lima
Conselho Nacional de Desenvolvimento Científico e Tecnológico (471283/2012-6)
- Thiago S Moreira
Conselho Nacional de Desenvolvimento Científico e Tecnológico (301651/2013-2)
- Ana C Takakura
Conselho Nacional de Desenvolvimento Científico e Tecnológico (301904/2015-4)
- Thiago S Moreira
Totman Medical Research Trust
- Mark T Nelson
Fondation Leducq
- Mark T Nelson
EC horizon 2020
- Mark T Nelson
Connecticut department of public health (150263)
- Daniel K Mulkey
Sao Paulo Research Foundation (2014/22406-1)
- Ana C Takakura
Conselho Nacional de Desenvolvimento Científico e Tecnológico (471263/2013-3)
- Ana C Takakura
National Institutes of Health (HL126381)
- Virginia E Hawkins
National Institutes of Health (HL095488)
- Mark T Nelson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All in vitro procedures were performed in accordance with National Institutes of Health and University of Connecticut Animal Care and Use Guidelines (protocol # A16-034). All in vivo procedures were performed in accordance with guidelines approved by the University of São Paulo Animal Care and Use Committee (protocol # 112/2015).
Reviewing Editor
- Jan-Marino Ramirez, Seattle Children's Research Institute and University of Washington, United States
Publication history
- Received: January 18, 2017
- Accepted: April 6, 2017
- Accepted Manuscript published: April 6, 2017 (version 1)
- Accepted Manuscript updated: April 7, 2017 (version 2)
- Version of Record published: May 8, 2017 (version 3)
Copyright
© 2017, Hawkins et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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