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

Knight, W. David; Little, Joel T.; Carreño, Flávia Regina; Toney, Glenn M.; Mifflin, Steve; Cunningham, J. Thomas

doi:10.1152/ajpregu.00830.2010

Cited by 86 publications

(125 citation statements)

References 59 publications

(89 reference statements)

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“…Their brains were removed and placed in 4% paraformaldehyde for 2 h and transferred to 30% sucrose in PBS. After 2-3 days, serial coronal forebrain sections (40 m) were collected using a cryostat (Leica Biosystems, Buffalo Grove, IL) and stored in cryoprotectant at Ϫ20°C until processed further for either c-Fos [1:2,000; goat anti-c-Fos (sc-52-G), Santa Cruz Biotechnologies, Santa Cruz, CA] or glial fibrillary acidic protein (GFAP) [1:1,000 mouse monoclonal anti-GFAP (clone G3893), Sigma-Aldrich] immunohistochemistry according to previously described methods (25).…”

Section: Ang Ii-induced Drinking Response and C-fos Expression Experimentioning

confidence: 99%

“…After 7 days of recovery from stereotaxic surgery, each rat was anesthetized (isoflurane 2%) and implanted with an abdominal aortic catheter, attached to a radiotelemetry transmitter (model TA11PA-C40) as previously described (7,25). The rats were allowed to recover for an additional 7 days from the surgery.…”

Section: Telemetry Monitoring Of Blood Pressure Heart Rate Respiratmentioning

confidence: 99%

“…For CIH treatments, the rats' home cages were placed in custombuilt Plexiglas chambers containing O 2 monitors and connected to a custom-made set of time-controlled valves used to expose the rats to 6-min cycles of 10% O 2 as previously described (25). These hypoxianormoxia cycles were repeated for 8 h during the light (nocturnal) phase, from 0800 to 1600.…”

Section: Cih Protocolmentioning

confidence: 99%

“…One set of forebrain sections from each rat was processed for FosB (goat anti-FosB, Santa Cruz Biotechnology; 1:1,000) immunohistochemistry as previously described (25). As the antibody binds with both FosB and its splice variant ⌬FosB, we refer to the resultant staining as FosB/⌬FosB.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…ANG II actions on the SFO are known to promote drinking behavior (31,45) and salt appetite (53). In addition, the SFO has also been shown to participate in ANG II-dependent hypertension (23,55), and we previously observed that the SFO may be chronically activated during CIH (25). On the basis of these observations, we tested whether the SFO, as an important site of action for peripheral ANG II, is involved in CIH hypertension.…”

mentioning

confidence: 99%

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Angiotensin II type 1a receptors in subfornical organ contribute towards chronic intermittent hypoxia-associated sustained increase in mean arterial pressure

Saxena

Little

Nedungadi

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Saxena A, Little JT, Nedungadi TP, Cunningham JT. Angiotensin II type 1a receptors in subfornical organ contribute towards chronic intermittent hypoxia-associated sustained increase in mean arterial pressure. Am J Physiol Heart Circ Physiol 308: H435-H446, 2015. First published December 24, 2014 doi:10.1152/ajpheart.00747.2014.-Sleep apnea is associated with hypertension. The mechanisms contributing to a sustained increase in mean arterial pressure (MAP) even during normoxic awake-state remain unknown. Rats exposed to chronic intermittent hypoxia for 7 days, a model of the hypoxemia associated with sleep apnea, exhibit sustained increases in MAP even during the normoxic dark phase. Activation of the renin-angiotensin system (RAS) has been implicated in chronic intermittent hypoxia (CIH) hypertension. Since the subfornical organ (SFO) serves as a primary target for the central actions of circulating ANG II, we tested the effects of ANG II type 1a receptor (AT1aR) knockdown in the SFO on the sustained increase in MAP in this CIH model. Adeno-associated virus carrying green fluorescent protein (GFP) and small-hairpin RNA against either AT1aR or a scrambled control sequence (SCM) was stereotaxically injected in the SFO of rats. After recovery, MAP, heart rate, respiratory rate, and activity were continuously recorded using radiotelemetry. In the normoxic groups, the recorded variables did not deviate from the baseline values. Both CIH groups exhibited significant increases in MAP during CIH exposures (P Ͻ 0.05). During the normoxic dark phase in the CIH groups, only the SCMinjected group exhibited a sustained increase in MAP (P Ͻ 0.05). The AT1aR-CIH group showed significant decreases in FosB/⌬FosB staining in the median preoptic nucleus and the paraventricular nuclei of the hypothalamus compared with the SCM-CIH group. Our data indicate that AT1aRs in the SFO are critical for the sustained elevation in MAP and increased FosB/⌬FosB expression in forebrain autonomic nuclei associated with CIH. angiotensin receptor; subfornical organ; chronic intermittent hypoxia; obstructive sleep apnea; AT1aR SLEEP APNEA (SA) is increasingly being recognized as a cause of neurogenic and treatment-resistant hypertension (12,19,32,37,52). SA is associated with a sustained increase in sympathetic nerve activity (SNA) and mean arterial pressure (MAP) even during periods of wakefulness and normoxia (4, 33). Animal models of chronic intermittent hypoxia (CIH), such as the one introduced by Fletcher at al. (17), produce cardiovascular sequelae similar to sleep apnea (11). Together, it appears that CIH episodes lead to pathophysiological adaptations that may generate and sustain a heightened basal MAP, which is partially dependent on increased SNA.The renin-angiotensin system (RAS) is activated during CIH (11,16,54), and it contributes to CIH hypertension (11, 16). For example, in rats exposed to CIH, peripheral administration of losartan, an angiotensin II (ANG II) type 1 receptor (AT1R) antagonist, has been shown to prevent the increase ...

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Section: Ang Ii-induced Drinking Response and C-fos Expression Experimentioning

confidence: 99%

Section: Telemetry Monitoring Of Blood Pressure Heart Rate Respiratmentioning

confidence: 99%

Section: Cih Protocolmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

mentioning

confidence: 99%

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Angiotensin II type 1a receptors in subfornical organ contribute towards chronic intermittent hypoxia-associated sustained increase in mean arterial pressure

Saxena

Little

Nedungadi

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Peripheral Chemoreception and Arterial Pressure Responses to Intermittent Hypoxia

Prabhakar

Peng

Kumar

et al. 2015

Comprehensive Physiology

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Carotid bodies are the principal peripheral chemoreceptors for detecting changes in arterial blood oxygen levels, and the resulting chemoreflex is a potent regulator of blood pressure. Recurrent apnea with intermittent hypoxia (IH) is a major clinical problem in adult humans and infants born preterm. Adult patients with recurrent apnea exhibit heightened sympathetic nerve activity and hypertension. Adults born preterm are predisposed to early onset of hypertension. Available evidence suggests that carotid body chemoreflex contributes to hypertension caused by IH in both adults and neonates. Experimental models of IH provided important insights into cellular and molecular mechanisms underlying carotid body chemoreflex-mediated hypertension. This article provides a comprehensive appraisal of how IH affects carotid body function, underlying cellular, molecular, and epigenetic mechanisms, and the contribution of chemoreflex to the hypertension.

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Neural Control of the Upper Airway: Respiratory and State‐Dependent Mechanisms

Kubin

2016

Comprehensive Physiology

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Upper airway muscles subserve many essential for survival orofacial behaviors, including their important role as accessory respiratory muscles. In the face of certain predisposition of craniofacial anatomy, both tonic and phasic inspiratory activation of upper airway muscles is necessary to protect the upper airway against collapse. This protective action is adequate during wakefulness, but fails during sleep which results in recurrent episodes of hypopneas and apneas, a condition known as the obstructive sleep apnea syndrome (OSA). Although OSA is almost exclusively a human disorder, animal models help unveil the basic principles governing the impact of sleep on breathing and upper airway muscle activity. This article discusses the neuroanatomy, neurochemistry, and neurophysiology of the different neuronal systems whose activity changes with sleep-wake states, such as the noradrenergic, serotonergic, cholinergic, orexinergic, histaminergic, GABAergic and glycinergic, and their impact on central respiratory neurons and upper airway motoneurons. Observations of the interactions between sleep-wake states and upper airway muscles in healthy humans and OSA patients are related to findings from animal models with normal upper airway, and various animal models of OSA, including the chronic-intermittent hypoxia model. Using a framework of upper airway motoneurons being under concurrent influence of central respiratory, reflex and state-dependent inputs, different neurotransmitters, and neuropeptides are considered as either causing a sleep-dependent withdrawal of excitation from motoneurons or mediating an active, sleep-related inhibition of motoneurons. Information about the neurochemistry of state-dependent control of upper airway muscles accumulated to date reveals fundamental principles and may help understand and treat OSA.

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

Cited by 86 publications

References 59 publications

Angiotensin II type 1a receptors in subfornical organ contribute towards chronic intermittent hypoxia-associated sustained increase in mean arterial pressure

Angiotensin II type 1a receptors in subfornical organ contribute towards chronic intermittent hypoxia-associated sustained increase in mean arterial pressure

Peripheral Chemoreception and Arterial Pressure Responses to Intermittent Hypoxia

Neural Control of the Upper Airway: Respiratory and State‐Dependent Mechanisms

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