The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension

McBryde, Fiona D; Abdala, Ana Paula; Hendy, Emma B; Pijacka, Wioletta; Marvar, Paul J.; Moraes, Davi J. A.; Sobotka, Paul; Paton, Julian F. R.

doi:10.1038/ncomms3395

Cited by 224 publications

(277 citation statements)

References 60 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%

“…Our results showing that ibuprofen reduced the c-fos immunoreactivity in NTS neurons support a novel role for inflammation in the hypertension induced by CIH. 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.…”

Section: Perspectivesmentioning

confidence: 99%

“…Moreover, our results demonstrate that the CB plays a pivotal role in the development of CIH-induced cardiac arrhythmias. The CB has been involved in several human sympathetic-mediated diseases, and the denervation or selective ablation of the CBs has been proposed as a feasible clinical treatment for severe and resistant hypertension in humans 49,50 and cardiovascular consequences of heart failure. 30 Thus, it is possible that the modulation of the enhanced CB function will be of therapeutic value to develop new treatments intended to improve the cardiovascular consequences of OSA.…”

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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: Perspectivesmentioning

confidence: 99%

mentioning

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 levels of lncRNAs were normalized to GAPDH and expressed as fold of change compared to control group. [34,35]. Cheng et al indicated that acid-sensing ion channel 3, but not capsaicin receptor TRPV1, played a protective role in isoproterenol-induced myocardial ischemia in mice [36].…”

Section: Discussionmentioning

confidence: 99%

Altered myocardial gene expression profiling in the ischemic tissues at different time points after cardiac ischemia/reperfusion in rats

Li¹,

Lin²,

He³

et al. 2018

Oncotarget

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We used Agilent Gene Expression microarray to analyze differential gene and lncRNA expression patterns in the myocardial ischemia regions during ischemia/ reperfusion (I/R)-induced cardiac injury in rats. Male SD rats were assigned into control group, 2 h group (30 min ischemia followed by 2 h reperfusion), 0.5 h (30 min ischemia followed by 0.5h reperfusion) group. We observed that of 18090 lncRNAs, an average of 233 lncRNAs was up-regulated in ischemic tissues of 2 h group, compared with those in control group, while an average of 6115 lncRNAs was down-regulated (with a > 2.0 fold-change and p < 0.05). Further, a total of 3135 mRNAs were differentially expressed between control group and 2h group, in which 542 mRNAs were up-regulated and 2593 mRNAs were down-regulated. Some differentially expressed genes were validated by qRT-PCR analyses of select lncRNAs in different time points after cardiac I/R injury. We unveiled that the expressions of lncRNA XR_345533.2, NONRATT025386, NONRATT024318, XR_599241.1, and NONRATT025509 were significantly up-regulated in 2h group compared with control group and 0.5h group, whereas the expression of lncRNA NR_130708.1 was downregulated after cardiac I/R injury and had no statistically different between 0.5h group and 2h group. Otherwise, the expressions of lncRNA NONRATT028627, NONRATT021959, XR_590005.1 and NONRATT023191 were significantly up-regulated in 2h group compared with 0.5h group. These findings provide evidence for differential expression patterns of mRNAs and lncRNAs in the ischemic tissues after cardiac I/R injury in rats.

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“…97 The results from the first in -human proof of concept study of a total of 15 patients with RH who underwent unilateral carotid body removal came from Gdansk's group. 98 Histology material revealed the finding of glomus cells in resected tissue in 14 out of 15 treated patients confirming the feasibility of the surgical approach.…”

Section: Carotid Body Denervationmentioning

confidence: 99%

Recent advances in the pathophysiology of arterial hypertension - potential implications for clinical practice

Hering¹,

Trzebski²

2017

Polish Archives of Internal Medicine

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REVIEW ARTICLE Advances in pathophysiology of arterial hypertension 195 population. Notably, only 46.5% of participants were aware of their hypertension, with less than half (40.6%) medically treated and BP levels less than 140/90 mm Hg achieved in 1 in 3 individuals (13.2%).1 The global disparities in the prevalence, awareness, treatment, and control of hypertension have also been indicated in a recent meta -analysis of 135 population -based studies from 90 countries.2 Globally, the number of individuals with hypertension increased, reaching an estimated total of 1.39 billion adults with hypertension, including 349 million in high -income countries and 1.04 billion in low-and middle -income countries by 2010. The increased and highest prevalence of raised BP has been particularly noted in East Europe, Asia, Africa, and Latin America. 2 Introduction Despite the well -recognized benefits of reducing major cardiovascular events and mortality through the control of blood pressure (BP), detection rates and control of hypertension remain low across all countries. Even though therapy is initiated in the vast majority of patients diagnosed with hypertension, treatment is suboptimal with a declined use of antihypertensive drugs over time. A large gap between the prevalence, awareness, treatment, and control of hypertension has been addressed in the multinational Prospective Urban Rural Epidemiology (PURE) study conducted in 628 communities, including high -income, upper -middle -income, low -middle -income and low -income countries. KEY WORDShypertension, interventional therapies, neural reflexes, neuroplasticity, sympathetic nervous system ABSTRACT Hypertension remains a major and growing public health problem associated with the greatest global rate of cardiovascular morbidity and mortality. Although numerous factors contribute to poor control of blood pressure (BP) and to pseudo resistance (eg, unawareness, lifestyle habits, nonadherence to medication, insufficient treatment, drug -induced hypertension, undiagnosed secondary causes), true resistant hypertension (RH) is reported in 10.1% of patients treated for elevated BP. While the mechanisms underlying RH remain complex and not entirely understood, sympathetic activation involved in the pathophysiology of hypertension, disease progression, and adverse complications is further augmented in patients with drug -resistant hypertension. The well -established contribution of neurogenic component of hypertension has led to the introduction of new alternative therapies aimed specifically at modulating central and neural reflexes mechanisms involved in BP control. Although clinical benefits of lowering BP with renal denervation, baroreflex activation therapy, carotid body denervation, central arteriovenous anastomosis, and deep brain stimulation have advanced our knowledge on uncontrolled hypertension, the variable BP response has prompted extensive ongoing research to define predictors of treatment effectiveness and further investigation of pathophysiology of RH. Very rec...

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The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension

Cited by 224 publications

References 60 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

Altered myocardial gene expression profiling in the ischemic tissues at different time points after cardiac ischemia/reperfusion in rats

Recent advances in the pathophysiology of arterial hypertension - potential implications for clinical practice

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