Ventilatory plasticity induced by episodic hypercapnic stimulation in heart failure (HF) is retrotrapezoid nucleus (RTN) chemoreceptor neuron-dependent. A: schematic of episodic hypercapnic stimulation (EHS) paradigm (top panel). Effect of EHS on ventilation (ΔRf) during pre- and post-EHS phases. Note that during the post-EHS phase, Sham+Veh rats showed ventilatory depression, and this effect was absent in HF+Veh rats. Selective ablation of RTN neurons by substance P-conjugated saporin (SSP-SAP) toxin normalizes the post-EHS ventilatory response in HF rats. B: representative traces of ventilation pre- and post-EHS in all experimental groups. C–E: summary data of tidal volume (ΔVT), respiratory frequency (ΔRf), and minute ventilation (ΔV̇e) during post-EHS phase, respectively. Data represent mean ± SE (A) while box and whiskers represent median ± range (C–E). One-way ANOVA followed by Holm-Sidak post hoc test; n = 6 rats per group. *P < 0.05 vs. Sham+Veh; +P < 0.05 vs. HF+Veh.