Fos expression by glutamatergic neurons of the solitary tract nucleus after phenylephrine‐induced hypertension in rats

Abstract

The baroreflex pathway might include a glutamatergic connection between the nucleus of the solitary tract (NTS) and a segment of the ventrolateral medulla (VLM) called the caudal ventrolateral medulla. The main goal of this study was to seek direct evidence for such a connection. Awake rats were subjected to phenylephrine- (PE-) induced hypertension (N=5) or received saline (N=5). Neuronal activation was gauged by the presence of Fos-immunoreactive (Fos-ir) nuclei. Fos-ir neurons that contained vesicular glutamate transporter 2 mRNA (glutamatergic neurons) or glutamic acid decarboxylase mRNA (GABAergic neurons) were mapped throughout the medulla oblongata. Saline-treated rats had very few Fos-ir neurons. In PE-treated rats, Fos-ir neurons were detected in both NTS and VLM. In NTS, 72% of Fos-ir neurons were glutamatergic and 26% were GABAergic. In the VLM, 41% of Fos-ir neurons were glutamatergic and 56% were GABAergic. In VLM, Fos-ir glutamatergic neurons were evenly distributed and were often catecholaminergic, whereas Fos-ir GABAergic cells were clustered around Bregma -13.0 mm. This region of the VLM was injected with Fluoro-Gold (FG) in eight rats, four of which received PE and the rest saline. Fos-ir NTS neurons retrogradely labeled with FG were detected only in PE-treated rats. These cells were exclusively glutamatergic and were concentrated within the NTS subnuclei that receive the densest inputs from arterial baroreceptors. In conclusion, PE, presumably via baroreceptor stimulation, induces Fos in glutamatergic and GABAergic neurons in both NTS and VLM. At least 29% of the Fos-ir glutamatergic neurons of NTS project to the vicinity of the VLM GABAergic interneurons that are presumed to mediate the sympathetic baroreflex.

Cranial Visceral Afferent Pathways through the Nucleus of the Solitary Tract to Caudal Ventrolateral Medulla or Paraventricular Hypothalamus: Target-Specific Synaptic Reliability and Convergence Patterns

“…This region of the NTS receives dense innervation from vagal afferents, including arterial baroreceptors (Ciriello, 1983;Mendelowitz et al, 1992), and also contains neurons that project to either CVLM or PVN (Weston et al, 2003;Hermes et al, 2006). Vagal afferent labeling was intense within ST, and varicose fibers were found in most subnuclei of NTS (Fig.…”

“…Neurons in these two regions display qualitatively different responses to baroreceptor afferent activation. CVLM neurons often display activity patterns that closely follow the pressure profile of each cardiac cycle (Jeske et al, 1993;Schreihofer and Guyenet, 2003), and raising blood pressure activates c-Fos in medial NTS neurons that send axons to CVLM (Weston et al, 2003). Such cardiovascular rhythms and baroreceptor responsiveness are only observed in a subpopulation of spinally projecting PVN neurons (Chen and Toney, 2003), whereas activation of arterial baroreceptors evokes few activity changes in most PVN neurons (Kannan and Yamashita, 1983; Duan et al, 1999).…”

Inhibition of Rac1-Derived Reactive Oxygen Species in Nucleus Tractus Solitarius Decreases Blood Pressure and Heart Rate in Stroke-Prone Spontaneously Hypertensive Rats

“…12,16 ROS in the brain are thought to contribute to the neuropathogenesis of hypertension by enhancing sympathetic nervous system activity. NAD(P)H oxidase is the source of ROS in the brain.…”

“…8,9 The nucleus tractus solitarius (NTS) in the brain stem has an important role in cardiovascular regulation. 10 -16 The NTS receives afferent input from baroreceptors and chemoreceptors 12 and has reciprocal interconnections with other nuclei involved in central autonomic regulation. 17 In addition, the essential NAD(P)H oxidase subunit gp91 phox is present in somatodendritic and axonal profiles that contain angiotensin II (Ang II) subtype 1 receptors in the NTS, and Ang II increases ROS generation via NAD(P)H oxidase in NTS neurons in vitro.…”

Changes in the subcellular distribution of NADPH oxidase subunit p47phox in dendrites of rat dorsomedial nucleus tractus solitarius neurons in response to chronic administration of hypertensive agents

“…We compared the effects of AngII on p47 phox trafficking with phenylephrine. The latter agent is a peripherally acting alpha1-adrenergic receptor agonist that elevates systemic blood pressure (31), and can affect activity of central cardiovascular pathways involving the NTS (50). When administered over a seven day period, AngII produces an elevation of systemic arterial pressure that is modest, slow, and not sufficient to produce cerebral, cardiac, or renal complications (49).…”