Selective inhibition of the adrenergic C1 neurons reduces the hypoxic ventilatory response in unanesthetized rats

Abstract

The catecholaminergic (TH) neurons that reside in the rostral half of the ventrolateral medulla (VLM), also called C1 neurons, regulate blood pressure, the CRF/ACTH/corticosterone cascade and autonomic glucoprivic responses. The stimuli that most commonly activates the C1 neurons (nociception, hypotension, and hypoxia) also increases breathing. Although pharmacological evidence suggests that catecholaminergic neurons regulate breathing, a specific contribution of the C1 neurons to respiratory control has not been demonstrated, particularly in vivo. Here, we evaluate the role of the C1 cells in the control of breathing under hypoxia (8% O2) or hypercapnia (7% CO2) condition in unanesthetized rats. Bilateral injection of the immunotoxin anti‐dopamine β‐hydroxylase‐saporin (anti‐DβH SAP) was done in adult unanesthetized male Wistar rats (270‐300g, N = 4‐7/group). Bilateral injections of anti‐DβH SAP (2.1 ng/100 nl) into VLM destroyed TH neurons. Selective inhibition of the C1 cells with bilateral injection of anti‐DβH‐SAP into the VLM reduced the increase in respiratory frequency (fR) (110 ± 5, vs. saline 136 ± 17 bpm), tidal volume (VT) (2.3 ± 0.2, vs. saline: 2.9 ± 0.3 ml/kg), and minute ventilation (MV) (244 ± 16, vs. saline: 402 ± 90 ml/kg/min) elicited by hypoxia (8% O2). Hypercapnia challenges (7% CO2) caused graded increases in fR, VT, and MV, however, the changes in breathing elicited by hypercapnia was not altered after selective destruction of C1 cells in the VLM. The present study indicates that C1 neurons could be involved in the regulation of breathing and provide evidence that they may contribute to the hypoxic ventilatory response.Financial support: FAPESP, CNPq, CAPES/PROEX.