Depletion of rostral ventrolateral medullary catecholaminergic neurons impairs the hypoxic ventilatory response in conscious rats

- Activation of C1 neurons increases sympathetic tone and ventilation.
- Ablation of C1 neurons did not affect cardiorespiratory control during rest or hypercapnia.
- Selective lesion of C1 neurons blunted ventilatory response to hypoxia and allowed BP to increase.
- We suggest that C1 neurons contribute to cardiorespiratory regulation during hypoxia.

The stimuli that commonly activate the catecholaminergic C1 neurons (nociception, hypotension, and hypoxia) also increase breathing. Pharmacogenetic evidence suggests that catecholaminergic neurons regulate breathing. Therefore, we evaluated whether the loss of C1 cells affects cardiorespiratory control during resting, hypoxic (8% O2) and hypercapnic (7% CO2) conditions. A bilateral injection of the immunotoxin anti-dopamine β-hydroxylase-saporin (anti-DβH-SAP; 2.4 ng/100 nl) or saline was performed in adult male Wistar rats (270-300 g, N = 5-8/group). Histology revealed a 60-75% loss of C1 neurons in anti-DβH-SAP-treated rats, but no significant changes or C1 cell loss was observed in sham-treated rats or those with off-target injection sites. Bilateral depletion of C1 neurons did not alter cardiorespiratory variables during rest and hypercapnia (7% CO2), but it did affect the response to hypoxia. Specifically, the increase in ventilation, the number of sighs, and the tachycardia were reduced, but unexpectedly, the mean arterial pressure increased during hypoxia (8% O2). The present study indicates that C1 neurons contribute to cardiorespiratory control during hypoxia rather than at rest or during hypercapnia.