Intermittent activation of peripheral chemoreceptors in awake rats induces Fos expression in rostral ventrolateral medulla–projecting neurons in the paraventricular nucleus of the hypothalamus

Abstract

Despite the well established sympathoexcitation evoked by chemoreflex activation, the specific sub-regions of the central nervous system underlying such sympathetic responses remain to be fully characterized. In the present study we examined the effects of intermittent chemoreflex activation in awake rats on Fos-immunoreactivity (Fos-ir) in various subnuclei of the paraventricular nucleus of the hypothalamus (PVN), as well as in identified neurosecretory preautonomic PVN neurons. In response to intermittent chemoreflex activation, a significant increase in the number of Fos-ir cells was found in autonomic-related PVN subnuclei, including the posterior parvocellular, ventromedial parvocellular and dorsal-cap, but not in the neurosecretory magnocellular-containing lateral magnocellular subnucleus. No changes in Fos-ir following chemoreflex activation were observed in the anterior PVN subnucleus. Experiments combining Fos immunohistochemistry and neuronal tract tracing techniques showed a significant increase in Fos-ir in rostral ventrolateral medulla (RVLM)-projecting (PVN-RVLM), but not in nucleus of solitarii tract (NTS)-projecting PVN neurons. In summary, our results support the involvement of the PVN in the central neuronal circuitry activated in response to chemoreflex activation, and indicate that PVN-RVLM neurons constitute a neuronal substrate contributing to the sympathoexcitatory component of the chemoreflex.

Chronic intermittent hypoxia increases blood pressure and expression of FosB/ΔFosB in central autonomic regions

“…Whereas areas such as NTS and PVN have been shown to be acutely influenced by carotid body chemoreceptor activation (6,8), increased FosB/⌬FosB staining was also observed in the lamina terminalis. A previous report on CNS effects of acute chemoreceptor activation or hypoxia did not report increased Fos staining in the lamina terminalis (8).…”

Acute systemic hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the caudal ventrolateral medulla

“…Activation (16,75) or disinhibition (61) of the PVN increases respiratory rate, MAP, and heart rate. Stimulation of peripheral chemoreceptors induces Fos immunoreactivity within PVN neurons (5), including magnocellular (66) and preautonomic neurons (9). In contrast, lesion or blockade of the PVN depresses ventilation and attenuates arterial chemoreceptor-mediated responses including increased arterial pressure, and sympathetic and phrenic nerve activity (49,54).…”

Renal Function and Fluid Homeostasis

“…Endogenous cardiac glycosides, which have Na + /K + -ATPase-inhibiting effects are secreted by the adrenal glands and hypothalamus in response to hypoxia, raise blood pressure and promote natriuresis [ 131 , 132 ]. These attributes make them attractive candidates in the peripheral chemoreceptor-mediated natriuretic response to hypoxia since there are afferent projections from the peripheral chemoreceptors to both these sites [ 133 ]. In hypoxemic patients with COPD, a plasma digoxin-like substance was elevated and correlated with urinary sodium excretion [ 134 ].…”