Directionally specific changes in arterial pressure induce differential patterns of fos expression in discrete areas of the rat brainstem: a double-labeling study for Fos and catecholamines.

Abstract

Although the nucleus tractus solitarii (NTS) has been established as the primary site of synaptic integration for the baroreceptor reflex, the higher-order pathways responsive to, and mediating, changes in vasomotor tone are not well characterized. We used immunohistochemistry to determine the distribution of cells expressing the Fos protein following pharmacologically induced, directionally specific changes in arterial pressure. The goal of this investigation was to determine if this immediate early gene product is differentially expressed in neurons of the rat brainstem following increased (pressor) versus decreased (depressor) arterial blood pressure (AP). Because brainstem catecholaminergic (CA) cell groups have been implicated in cardiovascular regulation, a double-labeling immunohistochemical procedure was used to examine the distribution of Fos in CA cells. Animals received continuous intravenous infusion of either a vasoconstrictor (l-phenylephrine hydrochloride), a vasodilator (sodium nitroprusside), or physiological saline. Extensive Fos-like immunoreactivity (FLI) was induced in both the pressor and depressor conditions in the NTS, caudal ventrolateral medulla (CVLM), rostral ventrolateral medulla (RVLM), A5, locus coeruleus (LC), Kolliker-Fuse, and parabrachial nucleus (PBN). These regions have all been implicated in central cardiovascular regulation. There were differences in the anatomical distribution of Fos-positive cells along the rostrocaudal axis of CVLM in the pressor and depressor conditions. Specifically, increased AP induced significantly more FLI cells within the rostral aspects of CVLM, whereas decreased AP resulted in a significantly greater number of FLI cells within the caudal CVLM. This result suggests that selective vasomotor responses differentially engaged discrete subsets of neurons within this brainstem region. Overall, approximately 50% of CA-immunoreactive cells were also FLI (CA-FLI) in the A1, A5, and A7 regions. Interestingly, increased AP produced significantly more CA-FLI double-labeled cells within the caudal than rostral A1 compared with depressor and control groups. Additionally, increased AP yielded significantly less CA-FLI double-labeled cells within the caudal A2 region. This suggests that CA barosensitive neurons in the CVLM/A1 and NTS/A2 regions are functionally segregated along the rostrocaudal axis of these structures. While twice as many PNMT-FLI double-labeled neurons were found in the C1-C3 regions following vasomotor changes versus saline control, there were no differences in the numbers or anatomical locations of labeled cells between pressor versus depressor groups. The results of this study indicate that (1) tonic changes in AP induce robust Fos expression in brainstem cardiovascular areas and (2) neurons responsive to specific directional changes in arterial pressure are segregated in some brainstem regions.