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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.<\/jats:p>","DOI":"10.7554\/elife.25232","type":"journal-article","created":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T08:03:25Z","timestamp":1491465805000},"source":"Crossref","is-referenced-by-count":53,"title":["Purinergic regulation of vascular tone in the retrotrapezoid nucleus is specialized to support the drive to breathe"],"prefix":"10.7554","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9505-6776","authenticated-orcid":true,"given":"Virginia E","family":"Hawkins","sequence":"first","affiliation":[{"name":"Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C","family":"Takakura","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Trinh","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milene R","family":"Malheiros-Lima","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin M","family":"Cleary","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C","family":"Wenker","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Dubreuil","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot M","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, University of Vermont, Burlington, United States"},{"name":"Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago S","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7040-3927","authenticated-orcid":true,"given":"Daniel K","family":"Mulkey","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2017,4,7]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"R1473","DOI":"10.1152\/ajpregu.91008.2008","article-title":"Integration of cerebrovascular CO2 reactivity and chemoreflex control of breathing: mechanisms of regulation, measurement, and interpretation","volume":"296","author":"Ainslie","year":"2009","journal-title":"American Journal of Physiology. 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