Delayed increase of tyrosine hydroxylation in the rat A2 medullary neurons upon long-term hypoxia

Abstract

In vivo and in vitro activity of tyrosine hydroxylase (TH) was estimated in the catecholaminergic A2 cell group of the nucleus tractus solitarius (NTS) in rats exposed to normobaric hypoxia (10% O 2 in nitrogen) for 2 h, 3, 7, 14 or 21 days. The A2 cell group was subdivided into two subgroups. In the caudal A2 subgroup located caudal to the calamus scriptorius, long-term but not acute hypoxia elicited an increase of in vivo tyrosine hydroxylation rate after 7 days of exposure (+ 60% above normoxic controls). The increase of in vivo TH activity was maintained at the same level at the end of hypoxic exposure. In vitro TH activity was increased transiently after 7 days of hypoxia (+ 92% above normoxic controls). In the rostral A2 subgroup, hypoxia elicited a significant increase of in vivo tyrosine hydroxylation at 7 days (+ 38%) but did not alter in vitro TH activity throughout the whole exposure. Hypoxia produced no detectable change in TH activity in other noradrenergic cell groups of the brain stem (locus coeruleus, A5) except for a transient inhibition of in vivo TH activity in A5 after 2 h. Immunocytochemical analyses confirmed that the catecholaminergic neurons in the caudal A2 area are only of a noradrenergic nature. These neurons were located in the commissural subnucleus of the NTS. On the other hand, the rostral A2 area contains noradrenergic neurons intermingled with a small number of adrenergic cell bodies. The data show that long-term hypoxia exerts a delayed stimulatory influence on the caudal A2 area, a discrete region which has been recognized as the main site of projection for chemosensory nerve fibers coming from peripheral arterial chemoreceptors. The delayed activation of TH suggests that noradrenergic neurons of the caudal A2 cell group may be involved in the central chemoreceptor pathway during long-term but not acute hypoxia.