Acute intermittent carotid body stimulations induce long‐term facilitation of respiratory–cardiovascular coupling in rats

Hypertension, the leading modifiable risk factor for global mortality, is driven in >50% of cases by neurogenic mechanisms linked to heightened sympathetic nerve activity (SNA). A hallmark of neurogenic hypertension is the exacerbation of respiratory-modulated SNA (RespSNA) and resulting blood pressure Traube-Hering (TH) waves, which emerges during the prehypertensive period and contributes to disease development. Carotid bodies (CBs), the peripheral chemoreceptors involved in the hypoxic response, are hyperactive in hypertensive patients and animal models. Their chronic intermittent stimulation, as seen in obstructive sleep apnoea, promotes hypertension characterised by exacerbated RespSNA and TH waves. Yet, their causal role in initiating these changes remains unclear. Here, we investigated whether acute intermittent CB stimulations could directly enhance RespSNA, TH waves and blood pressure from a physiological baseline, using the in situ working heart-brainstem preparation in rats. Four brief CB stimulations with sodium cyanide, mimicking acute intermittent hypoxia, were sufficient to induce a prolonged (>20 min) increase in both inspiratory and late expiratory RespSNA bursts, TH waves and perfusion pressure, with these effects being prevented by carotid sinus denervation. These changes were accompanied by a reconfiguration of central respiratory and cardiovascular control, including elevated respiratory heart rate variability and enhanced respiratory drive targeting upper airway and abdominal muscles. Our findings demonstrate that acute intermittent CB activation triggers sustained RespSNA and elevation of TH waves, supporting its potential role in development of hypertension. Our data also suggest that CBs play a key role in initiating this respiratory-cardiovascular plasticity and that central mechanisms might contribute to its long-term maintenance. KEY POINTS: Carotid body (CB) overactivity is implicated in sympathetic excitation and development of hypertension, but its direct role in initiating respiratory-cardiovascular dysfunction remains unresolved. We tested whether brief, repeated CB stimulations could trigger lasting changes in breathing and blood pressure control from a physiological baseline. In rats, only four stimulations induced a persistent increase in respiratory-modulated sympathetic activity, elevating blood pressure fluctuations (Traube-Hering waves) and mean blood pressure. These effects, prevented by carotid sinus denervation, were linked to enhanced respiratory-cardiovascular coupling and altered upper airway and abdominal motor control. Our findings reveal that short-term CB activation can induce long-term facilitation of respiratory-cardiovascular coupling, relevant to both physiological adaptations and hypertension pathogenesis.