Unilateral Vagotomy Blunts Cardiorespiratory Responses to Vagal Afferent Stimulation and Nucleus Tractus Solitarii (NTS) Glutamate Microinjection

Abstract

The nTS of the brainstem is the initial integration site of sensory information from the cardiorespiratory system, including afferents from the vagus nerve carrying input from the heart and lungs. The nTS is an important site of neuroplasticity, which depends on factors including neuronal and astrocytic activity, with the latter regulating glutamate (Glu) signaling. We have shown that unilateral transection of the vagus nerve to decrease afferent input results in morphologic changes in nTS glia. Vagal nerve transection also decreases nTS synaptic transmission studied in vitro. The influence of vagotomy on in vivo cardiorespiratory function via afferent‐driven Glu signaling is unknown. We hypothesized that chronic vagotomy blunts cardiorespiratory responses to vagal afferent stimulation via decreased Glu signaling. Male Sprague‐Dawley rats (6‐wk, N=19) were randomly assigned to vagotomy or sham groups. Right cervical vagus nerve transection caudal to the nodose ganglion or sham surgery was performed. One week after surgery, rats were anesthetized, ventilated, and instrumented to measure mean arterial pressure (MAP), heart rate (HR), splanchnic sympathetic and phrenic nerve activity (SSNA and PhrNA, respectively). Intact vagus nerves were transected acutely to prevent efferent stimulation. Left and right vagus nerves were stimulated (20 sec, 0.2mA, 2‐10Hz, 0.5ms pulse width) and responses recorded for 3 minutes. Chronic vagotomy had no effect on baseline cardiorespiratory parameters compared to shams. Vagal nerve stimulation on either side increased MAP, HR, and SSNA and decreased PhrNA in all groups. There were no consistent group differences in MAP, HR, and SSNA responses. However, chronic vagotomy blunted the stimulation‐induced decrease in PhrNA frequency and amplitude and decreased apnea duration on the ipsilateral side compared to contralateral stimulation and to shams. To evaluate the mechanism of altered respiratory responses, Glu was nanoinjected (30nL, 1‐10mM) into the left and right nTS of chronic vagotomy and sham rats. Glu decreased MAP, HR, SSNA, and PhrNA in all groups and on both sides. Chronic vagotomy had minimal effects on MAP and SSNA responses, but blunted the decrease in HR and PhrNA frequency and amplitude during ipsilateral Glu injection compared to contralateral. The blunted responses to vagal afferent stimulation and nTS glutamate suggest that chronic vagotomy alters Glu signaling in part via postsynaptic mechanisms. Additional experiments are needed to determine the mechanisms (including the role of astrocytes) of altered nTS Glu signaling to changes in afferent input in cardiorespiratory health and disease.