Alpha adrenergic receptor signaling in the hypothalamic paraventricular nucleus is diminished by the chronic intermittent hypoxia model of sleep apnea

Domingos-Souza, Gean; Martínez, Diana; Sinkler, Steven; Heesch, Cheryl M.; Kline, David D.

doi:10.1016/j.expneurol.2020.113517

Cited by 14 publications

(8 citation statements)

References 58 publications

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“…Next, we pre-treated C57BL/6J WT mice with phenylephrine (Phe), an α 1 AR agonist, before αGC administration. 34 This approach did not affect the overall development of a systemic pro-inflammatory response or the specific production of IFN-γ or TNF-α by iNKT cells induced by the in vivo administration of αGC ( Figures 6 A–6C). Despite high amounts of pro-inflammatory cytokines, no significant alterations in the ALT and AST levels were observed compared to control mice, in contrast to the αGC-treated group ( Figures 6 D and 6E).…”

Section: Resultsmentioning

confidence: 88%

Targeting adrenergic receptors to mitigate invariant natural killer T cells-induced acute liver injury

Gonzatti,

Freire,

Antunes

et al. 2023

iScience

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Section: Resultsmentioning

confidence: 88%

Targeting adrenergic receptors to mitigate invariant natural killer T cells-induced acute liver injury

Gonzatti,

Freire,

Antunes

et al. 2023

iScience

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“…Despite this low fidelity, exposure to moderate (≤12% O 2 ) hypoxia is a sufficient stimulus to activate brainstem catecholaminergic neurons that project to the PVN (King et al., 2012; King et al., 2013) and also PVN neurons (Smith et al., 1995). Furthermore, noradrenaline has multiple effects on PVN neurons (Domingos‐Souza et al., 2021; Li et al., 2005; Milanick et al., 2019) and lesioning brainstem catecholaminergic neurons that project to PVN blunts hypoxic ventilatory responses (King et al., 2015). Thus, a catecholaminergic projection from nTS to PVN appears critical to normal peripheral chemoreflex function.…”

Section: Discussionmentioning

confidence: 99%

Paraventricular nucleus projections to the nucleus tractus solitarii are essential for full expression of hypoxia‐induced peripheral chemoreflex responses

Ruyle,

Lima‐Silveira,

Martinez

et al. 2023

The Journal of Physiology

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The hypothalamic paraventricular nucleus (PVN) is essential to peripheral chemoreflex neurocircuitry, but the specific efferent pathways utilized are not well defined. The PVN sends dense projections to the nucleus tractus solitarii (nTS), which exhibits neuronal activation following a hypoxic challenge. We hypothesized that nTS‐projecting PVN (PVN‐nTS) neurons contribute to hypoxia‐induced nTS neuronal activation and cardiorespiratory responses. To selectively target PVN‐nTS neurons, rats underwent bilateral nTS nanoinjection of retrogradely transported adeno‐associated virus (AAV) driving Cre recombinase expression. We then nanoinjected into PVN AAVs driving Cre‐dependent expression of Gq or Gi designer receptors exclusively activated by designer drugs (DREADDs) to test the degree that selective activation or inhibition, respectively, of the PVN‐nTS pathway affects the hypoxic ventilatory response (HVR) of conscious rats. We used immunohistochemistry for Fos and extracellular recordings to examine how DREADD activation influences PVN‐nTS neuronal activation by hypoxia. Pathway activation enhanced the HVR at moderate hypoxic intensities and increased PVN and nTS Fos immunoreactivity in normoxia and hypoxia. In contrast, PVN‐nTS inhibition reduced both the HVR and PVN and nTS neuronal activation following hypoxia. To further confirm selective pathway effects on central cardiorespiratory output, rats underwent hypoxia before and after bilateral nTS nanoinjections of C21 to activate or inhibit PVN‐nTS terminals. PVN terminal activation within the nTS enhanced tachycardic, sympathetic and phrenic (PhrNA) nerve activity responses to hypoxia whereas inhibition attenuated hypoxia‐induced increases in nTS neuronal action potential discharge and PhrNA. The results demonstrate the PVN‐nTS pathway enhances nTS neuronal activation and is necessary for full cardiorespiratory responses to hypoxia. imageKey points The hypothalamic paraventricular nucleus (PVN) contributes to peripheral chemoreflex cardiorespiratory responses, but specific PVN efferent pathways are not known. The nucleus tractus solitarii (nTS) is the first integration site of the peripheral chemoreflex, and the nTS receives dense projections from the PVN. Selective GqDREADD activation of the PVN‐nTS pathway was shown to enhance ventilatory responses to hypoxia and activation (Fos immunoreactivity (IR)) of nTS neurons in conscious rats, augmenting the sympathetic and phrenic nerve activity (SSNA and PhrNA) responses to hypoxia in anaesthetized rats. Selective GiDREADD inhibition of PVN‐nTS neurons attenuates ventilatory responses, nTS neuronal Fos‐IR, action potential discharge and PhrNA responses to hypoxia. These results demonstrate that a projection from the PVN to the nTS is critical for full chemoreflex responses to hypoxia.

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“…In contrast, intra-PVN microinjection of prazosin decreased the systolic pressure and heart rate in previously undernourished adult hypertensive rats [ 24 , 93 ] altogether with lowering the spontaneous firing rate in PVN neurons [ 52 ]. In contrast, both noradrenaline and the α 1 -adrenoceptor agonist phenylephrine increased the frequency of spontaneous excitatory postsynaptic currents in PVN slices from normotensive control animals, but not in PVN slices from animals made hypertensive by chronic intermittent hypoxia [ 122 ].…”

Section: Maladaptive Programming Of Paraventricular-coerulear Network...mentioning

confidence: 99%

The Role of the Paraventricular-Coerulear Network on the Programming of Hypertension by Prenatal Undernutrition

Cayupe

Troncoso

Morgan

et al. 2022

IJMS

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A crucial etiological component in fetal programming is early nutrition. Indeed, early undernutrition may cause a chronic increase in blood pressure and cardiovascular diseases, including stroke and heart failure. In this regard, current evidence has sustained several pathological mechanisms involving changes in central and peripheral targets. In the present review, we summarize the neuroendocrine and neuroplastic modifications that underlie maladaptive mechanisms related to chronic hypertension programming after early undernutrition. First, we analyzed the role of glucocorticoids on the mechanism of long-term programming of hypertension. Secondly, we discussed the pathological plastic changes at the paraventricular nucleus of the hypothalamus that contribute to the development of chronic hypertension in animal models of prenatal undernutrition, dissecting the neural network that reciprocally communicates this nucleus with the locus coeruleus. Finally, we propose an integrated and updated view of the main neuroendocrine and central circuital alterations that support the occurrence of chronic increases of blood pressure in prenatally undernourished animals.

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Alpha adrenergic receptor signaling in the hypothalamic paraventricular nucleus is diminished by the chronic intermittent hypoxia model of sleep apnea

Cited by 14 publications

References 58 publications

Targeting adrenergic receptors to mitigate invariant natural killer T cells-induced acute liver injury

Targeting adrenergic receptors to mitigate invariant natural killer T cells-induced acute liver injury

Paraventricular nucleus projections to the nucleus tractus solitarii are essential for full expression of hypoxia‐induced peripheral chemoreflex responses

The Role of the Paraventricular-Coerulear Network on the Programming of Hypertension by Prenatal Undernutrition

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