Carotid Body Denervation Prevents the Development of Insulin Resistance and Hypertension Induced by Hypercaloric Diets

Ribeiro, Maria J.; Sacramento, Joana F.; González, C.; Guarino, Maria P.; Monteiro, Emília C.; Conde, Sílvia V.

doi:10.2337/db12-1463

Cited by 184 publications

(375 citation statements)

References 48 publications

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“…7,12,19,23,24 Recently, new experimental evidence has shown that the CB is involved in several sympathetic-mediated diseases. 7,[47][48][49][50][51] The selective ablation of the CB reduced BP in spontaneous hypertensive rats, 50 reduced sympathetic hyperactivation, improved survival in heart failure experimental models , 30,52 and prevented the development of hypertension and insulin resistance in rats fed with a highfat diet. 51 Thus, it is possible that the ablation of the CB will improve cardiovascular control in OSA.…”

Section: Discussionmentioning

confidence: 99%

“…7,[47][48][49][50][51] The selective ablation of the CB reduced BP in spontaneous hypertensive rats, 50 reduced sympathetic hyperactivation, improved survival in heart failure experimental models , 30,52 and prevented the development of hypertension and insulin resistance in rats fed with a highfat diet. 51 Thus, it is possible that the ablation of the CB will improve cardiovascular control in OSA. However, there is no available clinical information showing the effects of CB denervation in patients with OSA.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, McBryde et al 49 found that carotid sinus denervation in spontaneous hypertensive rats reduced CD3+ cells in single-cell suspensions of whole-brain stem homogenates, suggesting that CB denervation can reduce T-cellmediated infiltration of tissue, which is associated with several forms of hypertension. Thus, the ablation of the CBs, which improve rat survival in heart failure 30 and prevent the development of insulin resistance and hypertension in rats fed with high fructose diet, 51 has been proposed for the treatment of severe and resistant hypertension in humans. 49,50 Our findings indicate that CB ablation is an effective means for robust and sustained sympathoinhibition, which could translate to patients with neurogenic hypertension.…”

Section: Perspectivesmentioning

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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Perspectivesmentioning

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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“…Another rat study (Fletcher et al, 1992) reported how CBD eliminated the rise in blood pressure generated by chronic episodic hypoxia, such as is found in sleep apnea. Ribeiro et al (2013) demonstrate how CBD prevents the development of insulin resistance and hypertension induced by hypercaloric diets. The most comprehensive animal study with which we are familiar is that of Marcus and his colleagues in CHF rabbits (Marcus et al, 2014).…”

Section: Treatment Of the Target To Reduce Its Impactmentioning

confidence: 87%

Carotid Body: A New Target for Rescuing Neural Control of Cardiorespiratory Balance in Disease

2016

Frontiers Research Topics

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“…However, given the differences in OSA pathophysiology between the sexes, it will be challenging to extend the current design to obese men with insulin resistance who do not have OSA as these individuals are rare. It will also be of interest to determine if other contributors to OSA pathophysiology that have been implicated with insulin resistance such as heightened peripheral chemosensitivity [35] cause respiratory control instability during sleep and have a causal role in OSA pathogenesis and/or disease progression. Finally, the intriguing possibility that insulin "sensitisers" may improve upper airway collapsibility in patients with OSA and insulin resistance warrants further investigation.…”

Section: @Erspublicationsmentioning

confidence: 99%

When insulin has to work hard to keep the sugar at bay the upper airway collapses away

Eckert

Oliven

2016

Eur Respir J

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@ERSpublicationsInsulin resistance may increase upper airway collapsibility and directly contribute to sleep apnoea pathogenesis http://ow.ly/10BTf9Obesity is a major risk factor for both obstructive sleep apnoea (OSA) and metabolic disease. As obesity rates continue to rise, so too does the prevalence of OSA and metabolic disorders. Indeed, recent community sample data from over 2000 adults aged 40-85 years in Switzerland indicate that up to 50% of men and almost a quarter of women have apnoea-hypopnoea indices (AHI) within the moderate to severe range (>15 events·h −1 sleep) [1]. Insulin resistance, a strong predictor for the development of type 2 diabetes [2], is being recognised earlier with prevalence rates in children varying between 3 and 44% [3]. Thus, OSA and insulin resistance are major health issues.Given the shared link with obesity, the connection between metabolic disruption and OSA is not new. Indeed, OSA has been implicated in the pathogenesis of metabolic dysfunction [4][5][6]. Furthermore, a "bidirectional" or "reciprocal" relationship, or the possibility that OSA is a manifestation of the metabolic syndrome, has been discussed in several publications [7][8][9][10]. However, while evidence continues to grow that sleep-disordered breathing and sleep disruption can worsen metabolic function including insulin resistance [11], there is currently limited direct evidence to support the concept that early biomarkers of metabolic dysfunction such as insulin resistance predispose to OSA [12,13]. Thus, the chicken or the egg causality dilemma remains.The new study by LLANOS et al. [14] in this issue of the European Respiratory Journal takes us one step closer to solving this dilemma. Specifically, the authors have provided elegant insight into this question by going to the source; evaluating the relationship between pre-diabetes (i.e. insulin resistance), and "pre-OSA" (i.e. individuals with vulnerable upper airways due to high mechanical load from morbid obesity but without frank OSA (AHI <10 events/h sleep)). This unique approach has allowed the investigators to study upper airway collapsibility during sleep, using the gold standard critical closing pressure or "Pcrit" technique, without the confounding effects of prior exposure to repetitive severe hypoxaemia and sleep fragmentation, both of which contribute to metabolic sequelae [5,15]. Accordingly, consistent with insulin resistance preceding the decline in pharyngeal stability, the reported positive correlation between insulin resistance and upper airway collapsibility and the ∼4 cmH 2 O increase in Pcrit when the group was dichotomised according to high versus low insulin resistance cannot be explained by the presence of severe sleep-disordered breathing.

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Carotid Body Denervation Prevents the Development of Insulin Resistance and Hypertension Induced by Hypercaloric Diets

Cited by 184 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

Carotid Body: A New Target for Rescuing Neural Control of Cardiorespiratory Balance in Disease

When insulin has to work hard to keep the sugar at bay the upper airway collapses away

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