Sympathetic response to chemostimulation in conscious rats exposed to chronic intermittent hypoxia

Huang, Jianxiang; Lusina, Sara; Xie, Tian; Ji, En-Sheng; Xiang, Shuanglin; Liu, Yuzhen; Weiss, J. Woodrow

doi:10.1016/j.resp.2009.02.010

Cited by 46 publications

(43 citation statements)

References 27 publications

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“…An increase in HR during the hypoxic period is consistent with previous reports in rodents (18,30) and humans (14); however, other studies have not shown a change in HR after CIH (3-6, 9, 16, 22, 28). The increase in HR in response to CIH was seen in both HCR and LCR rats, suggesting (but not proving) a similar vagal and sympathetic response between these selected rat lines.…”

Section: Discussionsupporting

confidence: 92%

Rats selectively bred for differences in aerobic capacity have similar hypertensive responses to chronic intermittent hypoxia

Sharpe

Andrade

Herrera-Rosales

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Exposure to chronic intermittent hypoxia (CIH) is an animal model that mimics the repetitive bouts of hypoxemia experienced by humans with sleep apnea. Rats exposed to CIH develop hypertension that depends on the activation of sympathetic nerve activity (SNA). Since obesity and metabolic syndrome have been linked to neurogenic hypertension and sleep apnea, and because sleep apnea can adversely affect aerobic exercise capacity, we tested the hypothesis that rats bred for selection of low aerobic capacity running (LCR) would have a greater hypertensive response to CIH than rats bred for high aerobic capacity running (HCR). Blockade of ganglionic transmission was performed to compare the contribution of SNA to the maintenance of resting mean arterial pressure (MAP). Next, hypertensive responses to 7 days of CIH were compared across LCR and HCR rats (14-16 mo old). Finally, the contribution of the hypothalamic paraventricular nucleus (PVN) to the maintenance of SNA and hypertension after CIH was determined and compared across groups. Although LCR rats were less active and had greater body weights than HCR rats, resting MAP, the contribution of ongoing SNA to the maintenance of MAP, and hypertensive responses to CIH were similar between groups. Contrary to our hypothesis, chemical inhibition of the PVN with muscimol (1 mmol/100 nl) caused a larger fall of MAP in HCR rats than in LCR rats. We conclude that LCR rats do not have resting hypertension or an exaggerated hypertensive response to CIH. Interestingly, the maintenance of CIH hypertension in LCR rats compared with HCR rats appears less reliant on ongoing PVN neuronal activity.

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Section: Discussionsupporting

confidence: 92%

Rats selectively bred for differences in aerobic capacity have similar hypertensive responses to chronic intermittent hypoxia

Sharpe

Andrade

Herrera-Rosales

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…It is well known that hypoxic chemoreflex activation evokes baroreflex inhibition attributed to central nervous system modulation at the level of the nucleus of the solitary tract. 42,43 The hypertension induced by CIH is associated with reduced BRS efficiency in adult animals exposed to CIH for 1 to 3 months, 9,[11][12][13][14]40,41,44 but other studies performed in juvenile rats have shown that juvenile rats exposed to CIH for 15 days showed an increased cardiac baroreflex gain associated with a rightward shift on the operating point to higher pressures, as related to control rats. 38 Zoccal et al 38 proposed that the sympathetic-mediated hypertension is not secondary to a reduction in cardiac baroreflex gain, but to an enhanced respiratory-sympathetic coupling.…”

Section: Discussionmentioning

confidence: 96%

“…[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.…”

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confidence: 99%

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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“…Increased arterial pressure associated with CIH is dependent on SNA (2,34), the reninangiotensin system (13,16), and peripheral arterial chemoreceptors (14,34). CIH also alters central respiratory control (1,41,48), enhances SNA responses to acute hypoxia (17,29), and increases stress-induced adrenocorticotropic hormone release (36). While the effects of CIH on arterial chemoreceptor in the carotid bodies have been characterized (10,44), the central neural mechanisms responsible for persistent sympathoexcitation and elevation of blood pressure remain unclear.…”

mentioning

confidence: 99%

Chronic intermittent hypoxia increases blood pressure and expression of FosB/ΔFosB in central autonomic regions

Knight

Little

Carreño

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

117

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Chronic intermittent hypoxia (CIH) models repetitive bouts of arterial hypoxemia that occur in humans suffering from obstructive sleep apnea. CIH has been linked to persistent activation of arterial chemoreceptors and the renin-angiotensin system, which have been linked to chronic elevations of sympathetic nerve activity (SNA) and mean arterial pressure (MAP). Because Fos and FosB are transcription factors involved in activator protein (AP)-1 driven central nervous system neuronal adaptations, this study determined if CIH causes increased Fos or FosB staining in brain regions that regulate SNA and autonomic function. Male Sprague Dawley rats were instrumented with telemetry transmitters for continuous recording of MAP and heart rate (HR). Rats were exposed to continuous normoxia (CON) or to CIH for 8 h/day for 7 days. CIH increased MAP by 7-10 mmHg without persistently affecting HR. A separate group of rats was killed 1 day after 7 days of CIH for immunohistochemistry. CIH did not increase Fos staining in any brain region examined. Staining for FosB/ΔFosB was increased in the organum vasculosum of the lamina terminalis (CON: 9 ± 1; CIH: 34 ± 3 cells/section), subfornical organ (CON: 7 ± 2; CIH: 31 ± 3), median preoptic nucleus (CON 15 ± 1; CIH: 38 ± 3), nucleus of the solitary tract (CON: 9 ± 2; CIH: 28 ± 4), A5 (CON: 3 ± 1; CIH: 10 ± 1), and rostral ventrolateral medulla (CON: 5 ± 1; CIH: 17 ± 2). In the paraventricular nucleus, FosB/ΔFosB staining was located mainly in the dorsal and medial parvocellular subnuclei. CIH did not increase FosB/ΔFosB staining in caudal ventrolateral medulla or supraoptic nucleus. These data indicate that CIH induces an increase in FosB/ΔFosB in autonomic nuclei and suggest that AP-1 transcriptional regulation may contribute to stable adaptive changes that support chronically elevated SNA.

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Sympathetic response to chemostimulation in conscious rats exposed to chronic intermittent hypoxia

Cited by 46 publications

References 27 publications

Rats selectively bred for differences in aerobic capacity have similar hypertensive responses to chronic intermittent hypoxia

Rats selectively bred for differences in aerobic capacity have similar hypertensive responses to chronic intermittent hypoxia

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

Chronic intermittent hypoxia increases blood pressure and expression of FosB/ΔFosB in central autonomic regions

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