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 (PaC O 2 , Pa O 2 , pH, bicarbonate) and cardiorespiratory parameters in rats under baseline conditions and following anesthesia and vagotomy. Thirty minutes after urethane (1.2 g/kg, i.v.), heart rate (HR) and respiratory f R equency ( f R ) increased, while mean arterial pressure (MAP), tidal volume ( V T ), and ventilation ( V E ) decreased. Increased PaC O 2 , and reduced levels of pH and Pa O 2 were observed without changes in bicarbonate. Bilateral vagotomy further increased MAP, HR, and V T but reduced f R and V E , aggravating the increase in PaC O 2 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 CO 2 thresholds after vagotomy. Vagotomy also abolished phasic inhibition during inspiration and post-inspiration, 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.