Nitric oxide in the rostral ventrolateral medulla modulates hyperpnea but not anapyrexia induced by hypoxia

Hypoxia causes hyperpnea and anapyrexia (a regulated decrease in body temperature, T(b)) but the mechanisms involved are not well understood. The nitric oxide (NO) pathway is involved in hypoxia-induced anapyrexia and hyperpnea, but the site(s) of action is not known. Nitric oxide synthase is present in the rostral ventrolateral medulla (RVLM), which is a nucleus in the medulla oblongata involved in control of breathing, and RVLM neurons have been suggested to have intrinsic hypoxic chemosensitivity. Therefore, we examined the effects of inhibition of the NO pathway in the RVLM on hypoxic hyperpnea and anapyrexia. Ventilation (VE) and body temperature (T(b)) were measured before and after bilateral microinjection of N-monomethyl-L-arginine (L-NMMA, 12.5 microg/0.1 microl, a nonselective nitric oxide synthase inhibitor) into the RVLM, followed by a 120-min period of hypoxic exposure. Control rats received microinjection of saline (vehicle). Under normoxia, L-NMMA treatment did not affect VE or T(b). Typical hypoxia-induced hyperpnea and anapyrexia were observed after saline treatment. L-NMMA treatment reduced the ventilatory response to hypoxia but did not affect hypoxia-induced anapyrexia. These data suggest that nitric oxide in the RVLM is involved in the ventilatory response to hypoxia, exercising an excitatory modulation of the RVLM neurons, but plays no role in hypoxia-induced anapyrexia.