Ventilatory acclimatization to chronic hypoxia: relationship to noradrenaline metabolism in the rat solitary complex.
1. The relationship between ventilatory acclimatization to chronic hypoxia (10% O2-90% N2) and noradrenaline metabolism was examined in two regions located immediately caudal and rostral to the obex within the rat solitary complex. 2. Three experimental protocols were established. In protocol 1, the percentage changes in respiratory tidal volume, frequency and minute ventilation elicited by 4, 7, 10 and 14 days of hypoxia were assessed by flow plethysmography in awake rats, and then the content of tyrosine hydroxylase was measured in the solitary complex. In protocol 2, the time course response of tyrosine hydroxylase protein level was determined after 3, 7, 14 and 22 days of hypoxia by using a quantitative immunoblotting method for the protein assay. In protocol 3, the turnover of noradrenaline was estimated in the solitary complex after 14 days of hypoxia. 3. A progressive increase in ventilation was observed to reach a maximum (+105 +/- 15%, mean +/- S.E.M.) above normoxic control after 10 days of hypoxia, at which time it stabilized. Furthermore, tyrosine hydroxylase protein increased progressively and reached a maximal level at 14 days of hypoxia (+36 +/- 4%, mean +/- S.E.M.). Return to the basal level of tyrosine hydroxylase was observed after 22 days of hypoxia. 4. Tyrosine hydroxylase content (+36 +/- 4%) and noradrenaline turnover (+394 +/- 3%) increased exclusively in the caudal part of the solitary complex. 5. The ventilatory acclimatization to chronic hypoxia preceded the increase in tyrosine hydroxylase and these two parameters were significantly correlated. 6. These data suggest that ventilatory acclimatization to chronic hypoxia is associated with topical modifications of the brainstem catecholamine metabolism.
Schmitt
P
P
Laboratoire de Neuropharmacologie Moléculaire, UMR 105-CNRS, Faculté de Médecine, Lyon, France.
Soulier
V
V
Péquignot
J M
JM
Pujol
J F
JF
Denavit-Saubié
M
M
D000064:Acclimatization; D000818:Animals; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D017552:Solitary Nucleus / Q000201:enzymology / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine