Intermittent Hypoxia‐Induced Carotid Body Chemosensory Potentiation and Hypertension Are Critically Dependent on Peroxynitrite Formation

Moya, Esteban A.; Arias, Paulina; Carlos, Varela; Oyarce, María P.; Rio, Rodrigo Del; Iturriaga, Rodrigo

doi:10.1155/2016/9802136

Cited by 22 publications

(23 citation statements)

References 48 publications

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“…Indeed, the time course of the BP elevation is consistent with the time required by CIH to significantly enhance CB chemosensory output. 19,24,29 Compatible with this interpretation, we previously found that external carotid arteries segments harvested from rats exposed to CIH for 21 days, present moderate increases in the contractile responses to KCl and reduced NO-dependent relaxation induced by acetylcholine. 45 Thus, it is plausible that more pronounced vascular changes may take place if CIH is prolonged for >28 days.…”

Section: Del Rio Et Al Carotid Body and Intermittent Hypoxia-related mentioning

confidence: 80%

“…7,19,24,29 At day 21 of CIH, bilateral CB ablation was performed and rats were kept in CIH for 7 more days ( Figure S1 in the online-only Data Supplement).…”

Section: Experimental Protocolmentioning

confidence: 99%

“…28,29 Tidal volume (V T ), respiratory frequency (f R ), and minute volume (V I ) were determined by unrestrained wholebody plethysmography. Peripheral chemoreflex drive was evaluated as previously described.…”

Section: Cardiorespiratory Recordingsmentioning

confidence: 99%

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Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

et al. 2016

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The obstructive sleep apnea (OSA), a worldwide sleep breathing disorder that affect 9% of women and 24% of adult men, 1 is an independent risk factor for systemic hypertension and stroke and is associated with atrial arrhythmogenesis. [2][3][4][5][6] Chronic intermittent hypoxia (CIH), which is the principal feature of OSA, is considered the main factor for the hypertension.2-4,7 CIH produces autonomic dysfunction characterized by sympathetic hyperactivity, alterations of heart rate (HR) variability (HRV), and reduction of cardiac baroreflex efficiency. [8][9][10][11][12][13][14] Although the link between OSA and hypertension is well established, the mechanisms responsible for the autonomic imbalance and the hypertension are not entirely known. CIH produces oxidative stress, inflammation, and endothelial dysfunction that contribute to the hypertension. [2][3][4]7 However, a growing body of evidences suggests that the carotid body (CB), the main oxygen chemoreceptor organ, 15 plays a crucial role in the development of autonomic alterations and hypertension after CIH. Indeed, patients with OSA and animals exposed to CIH show enhanced cardiorespiratory and sympathetic responses to hypoxia, suggesting that CIH potentiates the CB-mediated chemoreflex drive. 7,13,[16][17][18][19] found that bilateral CB denervation before the CIH exposure prevents the development of the hypertension in rats. Despite this important result, the idea that the CB chemoreceptor contributes to the progression of cardiovascular pathologies associated with OSA was not seriously considered until the last decade. Indeed, in the last years, the proposal that the CB is involved in the progression of the CIH-induced hypertension received further attention . 3,4,7,18,21,22 Neural recordings of CB chemosensory activity have shown that CIH selectively Abstract-Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O 2 , 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments.In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and inc...

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Section: Del Rio Et Al Carotid Body and Intermittent Hypoxia-related mentioning

confidence: 80%

“…7,19,24,29 At day 21 of CIH, bilateral CB ablation was performed and rats were kept in CIH for 7 more days ( Figure S1 in the online-only Data Supplement).…”

Section: Experimental Protocolmentioning

confidence: 99%

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Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

et al. 2016

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“…Instead, our measurements of nitrotyrosine immunoreactivity reflect production of peroxynitrite, the rapidly-formed product of the interaction between superoxide and nitric oxide. Recently, evidence has emerged that CIH-induced sensitization of chemoreflex pathways is critically dependent on peroxynitrite (Moya et al, 2016). …”

Section: Discussionmentioning

confidence: 99%

“…We measured nitrotyrosine, a marker of the free radical oxidant, peroxynitrite, as an indicator of oxidative stress in carotid bodies (Del Rio et al, 2010, 2011a; Moya et al, 2016). At the end of 21 d of CIH or NORM exposures, the rats were deeply anesthetized with isoflurane and transcardially perfused with PBS to clear the red cells, followed by perfusion with 4% paraformaldehyde in PBS (300–500 ml, 25 ml/min).…”

Section: Methodsmentioning

confidence: 99%

Oxidative stress augments chemoreflex sensitivity in rats exposed to chronic intermittent hypoxia

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Río

et al. 2016

Respiratory Physiology & Neurobiology

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Chronic exposure to intermittent hypoxia (CIH) elicits plasticity of the carotid sinus and phrenic nerves via reactive oxygen species (ROS). To determine whether CIH-induced alterations in ventilation, metabolism, and heart rate are also dependent on ROS, we measured responses to acute hypoxia in conscious rats after 14 and 21 d of either CIH or normoxia (NORM), with or without concomitant administration of allopurinol (xanthine oxidase inhibitor), combined allopurinol plus losartan (angiotensin II type 1 receptor antagonist), or apocynin (NADPH oxidase inhibitor). Carotid body nitrotyrosine production was measured by immunohistochemistry. CIH produced an increase in the ventilatory response to acute hypoxia that was virtually eliminated by all three pharmacologic interventions. CIH caused a robust increase in carotid body nitrotyrosine production that was greatly attenuated by allopurinol plus losartan and by apocynin but unaffected by allopurinol. CIH caused a decrease in metabolic rate and a reduction in hypoxic bradycardia. Both of these effects were prevented by allopurinol, allopurinol plus losartan, and apocynin.

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A narrative review of the mechanisms and consequences of intermittent hypoxia and the role of advanced analytic techniques in pediatric autonomic disorders

et al. 2023

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Intermittent Hypoxia‐Induced Carotid Body Chemosensory Potentiation and Hypertension Are Critically Dependent on Peroxynitrite Formation

Cited by 22 publications

References 48 publications

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

Oxidative stress augments chemoreflex sensitivity in rats exposed to chronic intermittent hypoxia

A narrative review of the mechanisms and consequences of intermittent hypoxia and the role of advanced analytic techniques in pediatric autonomic disorders

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