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 CO2/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.