title: Role of nitric oxide in hypoxia-induced hyperventilation and hypothermia: participation of the locus coeruleus.
abstract: Hypoxia elicits hyperventilation and hypothermia, but the mechanisms involved are not well understood. The nitric oxide (NO) pathway is involved in hypoxia-induced hypothermia and hyperventilation, and works as a neuromodulator in the central nervous system, including the locus coeruleus (LC), which is a noradrenergic nucleus in the pons. The LC plays a role in a number of stress-induced responses, but its participation in the control of breathing and thermoregulation is unclear. Thus, in the present study, we tested the hypothesis that LC plays a role in the hypoxia-induced hypothermia and hyperventilation, and that NO is involved in these responses. Electrolytic lesions were performed bilaterally within the LC in awake unrestrained adult male Wistar rats weighing 250-350 g. Body temperature and pulmonary ventilation (V E) were measured. The rats were divided into 3 groups: control (N = 16), sham operated (N = 7) and LC lesioned (N = 19), and each group received a saline or an N G-nitro-L-arginine methyl ester (L-NAME, 250 microg/microl) intracerebroventricular (icv) injection. No significant difference was observed between control and sham-operated rats. Hypoxia (7% inspired O2) caused hyperventilation and hypothermia in both control (from 541.62 +/- 35.02 to 1816.18 +/- 170.7 and 36.3 +/- 0.12 to 34. 4 +/- 0.09, respectively) and LC-lesioned rats (LCLR) (from 694.65 +/- 63.17 to 2670.29 +/- 471.33 and 36 +/- 0.12 to 35.3 +/- 0.12, respectively), but the increase in V E was higher (P<0.05) and hypothermia was reduced (P<0.05) in LCLR. L-NAME caused no significant change in V E or in body temperature under normoxia, but abolished both the hypoxia-induced hyperventilation and hypothermia. Hypoxia-induced hyperventilation was reduced in LCLR treated with L-NAME. L-NAME also abolished the hypoxia-induced hypothermia in LCLR. The present data indicate that hypoxia-induced hyperventilation and hypothermia may be related to the LC, and that NO is involved in these responses.
authors.affiliation: Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: G
authors.initials: G
authors.lastname: Fabris
authors.forename: J A
authors.initials: JA
authors.lastname: Anselmo-Franci
authors.forename: L G
authors.initials: LG
authors.lastname: Branco
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006985:Hyperventilation / Q000209:etiology / Q000503:physiopathology*; D007035:Hypothermia / Q000209:etiology / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000150:complications / Q000503:physiopathology*; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester