title: 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 P2Y2/4receptors, 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.
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States.
authors.forename: Virginia E
authors.identifier: 0000-0001-9505-6776
authors.initials: VE
authors.lastname: Hawkins
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Takakura
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States.
authors.forename: Ashley
authors.initials: A
authors.lastname: Trinh
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Milene R
authors.initials: MR
authors.lastname: Malheiros-Lima
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States.
authors.forename: Colin M
authors.initials: CM
authors.lastname: Cleary
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Wenker
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States.
authors.forename: Todd
authors.initials: T
authors.lastname: Dubreuil
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States.
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Rodriguez
authors.affiliation: Department of Pharmacology, College of Medicine, University of Vermont, Burlington, United States.|Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Nelson
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Thiago S
authors.initials: TS
authors.lastname: Moreira
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States.
authors.forename: Daniel K
authors.identifier: 0000-0002-7040-3927
authors.initials: DK
authors.lastname: Mulkey
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D002245:Carbon Dioxide / Q000378:metabolism; D002560:Cerebrovascular Circulation; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011522:Protons; D051381:Rats; D011983:Receptors, Purinergic / Q000378:metabolism*; D012119:Respiration; D014664:Vasodilation
chemical_list: D011522:Protons; D011983:Receptors, Purinergic; D002245:Carbon Dioxide
keywords: ATP; arteriole; breathing; chemoreception; neuroscience; rat