Urethane and vagotomy reshape cardiorespiratory homeostasis and RTN chemoreceptor function.

Urethane anesthesia and vagotomy are common in neurophysiology but their impact on physiological homeostasis is not fully defined. We assessed arterial blood gases [arterial partial pressure of CO2 ([Formula: see text]), arterial partial pressure of O2 ([Formula: see text]), pH, and bicarbonate] and cardiorespiratory parameters in rats under baseline conditions and following anesthesia and vagotomy. Thirty minutes after urethane (1.2 g/kg, iv), heart rate (HR) and respiratory frequency (fR) increased, whereas mean arterial pressure (MAP), tidal volume (VT), and ventilation (V̇e) decreased. Increased [Formula: see text], and reduced levels of pH and [Formula: see text] were observed without changes in bicarbonate. Bilateral vagotomy further increased MAP, HR, and VT but reduced fR and V̇e, aggravating the increase in [Formula: see text] and acidosis. Artificial ventilation corrected blood gases but did not change the cardiovascular parameters. We next studied the activity of the retrotrapezoid nucleus (RTN) chemoreceptor neurons, because these neurons are involved in cardiorespiratory modulation. These neurons were activated by hypercapnia, inhibited by lung inflation, and displayed reduced CO2 thresholds after vagotomy. Vagotomy also abolished phasic inhibition during inspiration and postinspiration, producing peak activity during inspiration. These findings show that urethane anesthesia and vagotomy profoundly alter cardiorespiratory parameters and demonstrate that vagal inputs dynamically modulate RTN neuronal activity and central respiratory control. Together, these findings demonstrate that urethane anesthesia and vagotomy significantly alter baseline cardiorespiratory parameters and dynamically modulate RTN chemoreceptor activity, highlighting the importance of vagal feedback in central respiratory control.NEW & NOTEWORTHY Urethane anesthesia and vagotomy, common procedures in neurophysiology, profoundly alter baseline cardiorespiratory parameters and arterial blood gases. We show that vagotomy not only exacerbates hypercapnia and acidosis but also reshapes retrotrapezoid nucleus chemoreceptor activity, abolishing phasic inhibition and shifting peak activity to inspiration. These findings highlight the critical role of vagal feedback in central respiratory control and caution against overlooking the physiological consequences of standard experimental manipulations.