Activation of Retrotrapezoid Nucleus (RTN) Maintains Normal Breathing in Hyperoxia Despite the Loss of Carotid Body (CB) Input

Abstract

Rationale and objectives: the CBs contribute greatly to resting ventilation in conscious mammals. For example, their excision produces large and long‐lasting breathing reductions. Yet sustained hyperoxia, which silences the CBs, produces minimal breathing reductions in conscious rats and mildly activates breathing in man. RTN is a major cluster of central respiratory chemoreceptors (CRCs). Here we tested whether, under hyperoxia, breathing might be maintained by a compensatory increase in RTN activity.Methods: RTN and nearby C1 neurons were bilaterally transduced with archaerhodopsin (PRSx8‐ArchT‐EYFP‐LVV). We first showed that RTN neurons were instantly silenced by green light in anesthetized rats. We then measured the effect of RTN inhibition (10s) on breathing (fR, VT) and BP in conscious rats exposed to normoxia (21% FiO2) or hyperoxia (65% FiO2). Arterial blood gases (PO2, PCO2), pHa and HCO3 were measured under both conditions.Results: hyperoxia produced a very mild respiratory acidosis. RTN inhibition elicited a much larger fR and VT reduction in rats exposed to hyperoxia than to normoxia. BP was unaffected under hypoxia or hyperoxia suggesting that the C1 neurons were minimally impacted by the light.Interpretation: in conscious rats hyperoxia activates RTN, which maintains ventilation at control level (normoxia) despite the presumed loss of CB activity. RTN activation by hyperoxia probably results from several mechanisms including mild respiratory acidosis, Haldane effect and CNS vasoconstriction, the latter causing reduced CO2 wash‐out and brain parenchymal acidification. Funding: HL074011 (PGG), 5T32HL007284‐38 (TMB).