Breathing regulation and blood gas homeostasis after near complete lesions of the retrotrapezoid nucleus in adult rats

The retrotrapezoid nucleus (RTN) is one of several CNS nuclei that contribute, in various capacities (e.g. CO2 detection, neuronal modulation) to the central respiratory chemoreflex (CRC). Here we test how important the RTN is to PCO2 homeostasis and breathing during sleep or wake. RTN Nmb-positive neurons were killed with targeted microinjections of substance P-saporin conjugate in adult rats. Under normoxia, rats with large RTN lesions (92 +/- 4% cell loss) had normal blood pressure and arterial pH but were hypoxic (-8 mmHg PaO2) and hypercapnic (+10 mmHg ). In resting conditions, minute volume (V-E) was normal but breathing frequency (f(R)) was elevated and tidal volume (V-T) reduced. Resting O-2 consumption and CO2 production were normal. The hypercapnic ventilatory reflex in 65% FiO(2) had an inverse exponential relationship with the number of surviving RTN neurons and was decreased by up to 92%. The hypoxic ventilatory reflex (HVR; FiO(2) 21-10%) persisted after RTN lesions, hypoxia-induced sighing was normal and hypoxia-induced hypotension was reduced. In rats with RTN lesions, breathing was lowest during slow-wave sleep, especially under hyperoxia, but apnoeas and sleep-disordered breathing were not observed. In conclusion, near complete RTN destruction in rats virtually eliminates the CRC but the HVR persists and sighing and the state dependence of breathing are unchanged. Under normoxia, RTN lesions cause no change in V-E but alveolar ventilation is reduced by at least 21%, probably because of increased physiological dead volume. RTN lesions do not cause sleep apnoea during slow-wave sleep, even under hyperoxia.