Systemic inhibition of the Na(+)/H (+) exchanger type 3 in intact rats activates brainstem respiratory regions.
Selective inhibition of the Na(+)/H(+) exchanger type 3 (NHE3) increases the firing rate of brainstem ventrolateral CO(2)/H(+) sensitive neurons, resembling the responses evoked by hypercapnic stimuli. In anesthetized animals, NHE3 inhibition has also been shown to stimulate the central chemosensitive drive. We aimed to analyze the respiratory-related brainstem regions affected by NHE3 inhibition in anaesthetized spontaneously-breathing rats with intact peripheral afferents. For that, c-Fos immunopositive cells were counted along the brainstem in rats intravenously infused with the selective NHE3 inhibitor AVE1599. A rostral extension of the ventral respiratory column which includes the pre-Bötzinger complex was activated by the NHE3 inhibitor. In addition, the number of c-Fos positive cells resulted significantly increased in the most rostral extension of the retrotrapezoid nucleus/parapyramidal region. In the pons, the intravenous infusion of AVE1599 activated the lateral parabrachial and Kölliker-Fuse nuclei. Thus, selective NHE3 inhibition in anaesthetized rats activates the respiratory network and evokes a pattern of c-Fos expressing cells similar to that induced by hypercapnia.
Pasaro
R
R
Department of Physiology and Zoology, University of Seville, Seville, Spain. mrpasaro@us.es
Ribas-Salgueiro
J L
JL
Matarredona
E R
ER
Sarmiento
M
M
Ribas
J
J
D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*
D016760:Proto-Oncogene Proteins c-fos; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers