HEMODYNAMIC REGULATION OF TYROSINE-HYDROXYLASE MESSENGER-RNA IN MEDULLARY CATECHOLAMINE NEURONS - A C-FOS-GUIDED HYBRIDIZATION HISTOCHEMICAL-STUDY

Medullary catecholamine cell groups are involved in multiple modes of cardiovascular regulation and display indices of functional activation, including widespread c-fos expression, in response to hypotensive hemorrhage. Assessments of the impact of such challenges on transmitter-related gene expression are complicated by the biochemical and connectional heterogeneity that characterize these cell groups. Quantitative hybridization histochemical methods were used to follow the effects of 15% hemorrhage on levels of messenger RNA encoding tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, in medullary aminergic neurons; concurrent staining for nuclear Fos-immunoreactivity permitted comparisons between cells that ostensibly were and were not targeted by the challenge. Increased levels of tyrosine hydroxylase messenger RNA were detected in Fos-immunoreactive neurons in all cell groups examined. Mean maximal increases ranged between 133 and 192% of control values, and were attained within 0.5-1 h post-hemorrhage in noradrenergic (A1 and A2) cell groups, and at 2 h in adrenergic ones (C1, C2, and C2d or dorsal strip). By 4 h after the challenge, tyrosine hydroxylase messenger RNA levels in Fos-immunoreactive neurons in all cell groups had returned to control values. By contrast, tyrosine hydroxylase messenger RNA in non-Fos-immunoreactive cells either did not change significantly over the course of the experiment (C2 and C2d), or showed a rapid and transient increase, whose magnitude tended to be less than that seen in Fos-immunoreactive cells. c-fos messenger RNA was prominently induced in catecholaminergic neurons in each of the medullary cell groups examined at 0.5 h after hemorrhage, suggesting that the early tyrosine hydroxylase messenger RNA response to hemorrhage in non-Fos-immunoreactive cells preceded the capacity of responsive neurons to manifest detectable Fos protein expression. These findings indicate that hemorrhage up-regulates tyrosine hydroxylase messenger RNA levels in medullary catecholaminergic cell groups which have access to adaptive neuroendocrine and/or autonomic control systems. The approach employed here should prove of general utility in assessing the impact of environmental events on messenger RNA expression in connectionally heterogeneous cell groups that share a common biochemical phenotype.