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Breathing regulation and blood gas homeostasis after near complete lesions of the retrotrapezoid nucleus in adult rats
Author(s) -
Souza George M. P. R.,
Kanbar Roy,
Stornetta Daniel S.,
Abbott Stephen B.G.,
Stornetta Ruth L.,
Guyenet Patrice G.
Publication year - 2018
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp275866
Subject(s) - ventilation (architecture) , tidal volume , medicine , respiratory system , anesthesia , respiratory minute volume , hypoxia (environmental) , sleep and breathing , endocrinology , cardiology , chemistry , oxygen , mechanical engineering , organic chemistry , engineering
Key points The retrotrapezoid nucleus (RTN) drives breathing proportionally to brain P C O 2but its role during various states of vigilance needs clarification. Under normoxia, RTN lesions increased the arterial P C O 2set‐point, lowered the P O 2set‐point and reduced alveolar ventilation relative to CO 2 production. Tidal volume was reduced and breathing frequency increased to a comparable degree during wake, slow‐wave sleep and REM sleep. RTN lesions did not produce apnoeas or disordered breathing during sleep. RTN lesions in rats virtually eliminated the central respiratory chemoreflex (CRC) while preserving the cardiorespiratory responses to hypoxia; the relationship between CRC and number of surviving RTN Nmb neurons was an inverse exponential. The CRC does not function without the RTN. In the quasi‐complete absence of the RTN and CRC, alveolar ventilation is reduced despite an increased drive to breathe from the carotid bodies.Abstract The retrotrapezoid nucleus (RTN) is one of several CNS nuclei that contribute, in various capacities (e.g. CO 2 detection, neuronal modulation) to the central respiratory chemoreflex (CRC). Here we test how important the RTN is to PCO 2 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 PaO 2 ) 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 CO 2 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.