Role of the Autonomic Nervous System in the Acute Blood Pressure Elevation during Repetitive Hypoxic and Hypercapnic Breathing in Rats

Bakehe, M.; Hedner, Jan; Dang, Tze-Yu; Chambille, B; Gaultier, C; Escourrou, P.

doi:10.3109/08037059609078077

Cited by 8 publications

(4 citation statements)

References 16 publications

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“…Furthermore, and contrary to the marked increases in blood pressure associated with the Cushing reflex (13,50), hypoxic ventilatory depression in AMPK knockouts was associated with a fall in blood pressure equivalent to that of controls (see Figure E7) and wild-type mice (52). Notwithstanding these facts, hypoxia triggers increased blood pressure in both rats (53) and humans (54), and we cannot rule out the possibility that outcomes for blood pressure may reflect species-dependent variations allied to the Cushing reflex (50).…”

Section: Discussionmentioning

confidence: 84%

AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea

Mahmoud¹,

Lewis²,

Juričić³

et al. 2016

Am J Respir Crit Care Med

104

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Rationale: Modulation of breathing by hypoxia accommodates variations in oxygen demand and supply during, for example, sleep and ascent to altitude, but the precise molecular mechanisms of this phenomenon remain controversial. Among the genes influenced by natural selection in high-altitude populations is one for the adenosine monophosphate-activated protein kinase (AMPK) a1-catalytic subunit, which governs cell-autonomous adaptations during metabolic stress.Objectives: We investigated whether AMPK-a1 and/or AMPK-a2 are required for the hypoxic ventilatory response and the mechanism of ventilatory dysfunctions arising from AMPK deficiency.Methods: We used plethysmography, electrophysiology, functional magnetic resonance imaging, and immediate early gene (c-fos) expression to assess the hypoxic ventilatory response of mice with conditional deletion of the AMPK-a1 and/or AMPK-a2 genes in catecholaminergic cells, which compose the hypoxia-responsive respiratory network from carotid body to brainstem.Measurements and Main Results: AMPK-a1 and AMPK-a2 deletion virtually abolished the hypoxic ventilatory response, and ventilatory depression during hypoxia was exacerbated under anesthesia. Rather than hyperventilating, mice lacking AMPK-a1 and AMPK-a2 exhibited hypoventilation and apnea during hypoxia, with the primary precipitant being loss of AMPK-a1 expression. However, the carotid bodies of AMPK-knockout mice remained exquisitely sensitive to hypoxia, contrary to the view that the hypoxic ventilatory response is determined solely by increased carotid body afferent input to the brainstem. Regardless, functional magnetic resonance imaging and c-fos expression revealed reduced activation by hypoxia of well-defined dorsal and ventral brainstem nuclei.Conclusions: AMPK is required to coordinate the activation by hypoxia of brainstem respiratory networks, and deficiencies in AMPK expression precipitate hypoventilation and apnea, even when carotid body afferent input is normal.

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Section: Discussionmentioning

confidence: 84%

AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea

Mahmoud¹,

Lewis²,

Juričić³

et al. 2016

Am J Respir Crit Care Med

104

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“…30 for references). Certain forms of chronic intermittent hypoxia have been implicated in systemic hypertension (7,13,17), sudden infant death syndrome (5,32,38), and the pathological effects associated with obstructive sleep apnea (OSA; Ref. 34).…”

Section: Number Of Hypoxic Episodesmentioning

confidence: 99%

Effect of hypoxic episode number and severity on ventilatory long-term facilitation in awake rats

McGuire

Zhang

White

et al. 2002

Journal of Applied Physiology

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Episodic hypoxia induces a persistent augmentation of respiratory activity, termed long-term facilitation (LTF). Phrenic LTF saturates in anesthetized animals such that additional episodes of stimulation cause no further increase in LTF magnitude. The present study tested the hypothesis that 1) ventilatory LTF also saturates in awake rats and 2) more severe hypoxia and hypoxic episodes increase the effectiveness of eliciting ventilatory LTF. Minute ventilation was measured in awake, male Sprague-Dawley rats by plethysmography. LTF was elicited by five episodes of 10% O(2) poikilocapnic hypoxia (magnitude: 17.3 +/- 2.8% above baseline, between 15 and 45 min posthypoxia, duration: 45 min) but not 12 or 8% O(2). LTF was also elicited by 10, 20, and 72 episodes of 12% O(2) (19.1 +/- 2.2, 18.9 +/- 1.8, and 19.8 +/- 1.6%; 45, 60, and 75 min, respectively) but not by three or five episodes. These results show that there is a certain range of hypoxia that induces ventilatory LTF and that additional hypoxic episodes may increase the duration but not the magnitude of this response.

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“…The hypercapnia-induced pressor response is primarily a result of sympathetic mobilization that is mediated by chemoreceptors in the CNS (Elam et al, 1981, Fukuda et al, 1989Bakehe et al, 1996;Oikawa et al, 2005). As stated in introduction, ORX neurons are CO 2 chemosensitive, and ORX neurons can increase sympathetic outflow.…”

Section: Orx's Role In Hypercapnia-induced Pressor Responsesmentioning

confidence: 99%

Activation of the Orexin 1 Receptor is a Critical Component of CO2-Mediated Anxiety and Hypertension but not Bradycardia

Johnson

Samuels

Fitz

et al. 2012

Neuropsychopharmacol

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Acute hypercapnia (elevated arterial CO 2 /H + ) is a suffocation signal that is life threatening and rapidly mobilizes adaptive changes in breathing and behavioral arousal in order to restore acid-base homeostasis. Severe hypercapnia, seen in respiratory disorders (eg, asthma or bronchitis, chronic obstructive pulmonary disease (COPD)), also results in high anxiety and autonomic activation. Recent evidence has demonstrated that wake-promoting hypothalamic orexin (ORX: also known as hypocretin) neurons are highly sensitive to local changes in CO 2 /H + , and mice lacking prepro-ORX have blunted respiratory responses to hypercapnia. Furthermore, in a recent clinical study, ORX-A, which crosses blood-brain barrier easily, was dramatically increased in the plasma of patients with COPD and hypercapnic respiratory failure. This is consistent with a rodent model of COPD where chronic exposure to cigarette smoke led to a threefold increase in hypothalamic ORX-A expression. In the present study, we determined the role of ORX in the anxiety-like behavior and cardiorespiratory responses to acute exposure to a threshold panic challenge (ie, 20% CO 2 /normoxic gas). Exposing conscious rats to such hypercapnic, but not atmospheric air, resulted in respiratory, pressor, and bradycardic responses, as well as anxiety-like behavior and increased cellular c-Fos responses in ORX neurons. Systemically, pre-treating rats with a centrally active ORX1 receptor antagonist (30 mg/kg SB334867) attenuated hypercapnic gas-induced pressor and anxiety responses, without altering the robust bradycardia response, and only attenuated breathing responses at offset of the CO 2 challenge. Our results show that the ORX system has an important role in anxiety and sympathetic mobilization during hypercapnia. Furthermore, ORX1 receptor antagonists may be a therapeutic option rapidly treating increased anxiety and sympathetic drive seen during panic attacks and in hypercapnic states such as COPD.

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Role of the Autonomic Nervous System in the Acute Blood Pressure Elevation during Repetitive Hypoxic and Hypercapnic Breathing in Rats

Cited by 8 publications

References 16 publications

AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea

AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea

Effect of hypoxic episode number and severity on ventilatory long-term facilitation in awake rats

Activation of the Orexin 1 Receptor is a Critical Component of CO2-Mediated Anxiety and Hypertension but not Bradycardia

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