scholarly journals Vascular and renal telomere shortening in mice exposed to chronic intermittent hypoxia

2021 ◽  
Author(s):  
Mohammad Badran ◽  
Bisher Abuyassin ◽  
Najib Ayas ◽  
Don D. Sin ◽  
Ismail Laher
Keyword(s):  
Obstructive Sleep Apnea ◽  
Chronic Condition ◽  
Intermittent Hypoxia ◽  
Kidney Diseases ◽  
Chronic Intermittent Hypoxia ◽  
Telomere Shortening ◽  
Chronic Kidney Diseases ◽  
Biomarkers Of Aging ◽  
Obstructive Sleep ◽  
Renal Aging

AbstractObstructive sleep apnea (OSA) is a chronic condition characterized by chronic intermittent hypoxia (IH) and is associated with cardiovascular (CVD) and chronic kidney diseases (CKD). There is increased biomarkers of aging, such as telomere shortening, in patients with OSA. We assessed telomere lengths in aortic and renal tissues from mice exposed to 8 weeks of IH using a PCR protocol, and demonstrate significant telomere shortening in both tissues. This data indicates that IH, a hallmark of OSA, can accelerate vascular and renal aging that may contribute to OSA-induced CVD and CKD

scholarly journals Chronic Intermittent Hypoxia Induces the Long-Term Facilitation of Genioglossus Corticomotor Activity

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Zou ◽  
Wei Wang ◽  
Xinshi Nie ◽  
Jian Kang
Keyword(s):  
Obstructive Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Magnetic Stimulation ◽  
Upper Airway ◽  
Emg Activity ◽  
Chronic Intermittent Hypoxia ◽  
Experimental Conditions ◽  
Obstructive Sleep ◽  
Long Term Facilitation

Obstructive sleep apnea (OSA) is characterized by the repetitive collapse of the upper airway and chronic intermittent hypoxia (CIH) during sleep. It has been reported that CIH can increase the EMG activity of genioglossus in rats, which may be related to the neuromuscular compensation of OSA patients. This study aimed to explore whether CIH could induce the long-term facilitation (LTF) of genioglossus corticomotor activity. 16 rats were divided into the air group (n=8) and the CIH group (n=8). The CIH group was exposed to hypoxia for 4 weeks; the air group was subjected to air under identical experimental conditions in parallel. Transcranial magnetic stimulation (TMS) was applied every ten minutes and lasted for 1 h/day on the 1st, 3rd, 7th, 14th, 21st, and 28th days of air/CIH exposure. Genioglossus EMG was also recorded at the same time. Compared with the air group, the CIH group showed decreased TMS latency from 10 to 60 minutes on the 7th, 14th, 21st, and 28th days. The increased TMS amplitude lasting for 60 minutes was only observed on the 21st day. Genioglossus EMG activity increased only on the 28th day of CIH. We concluded that CIH could induce LTF of genioglossus corticomotor activity in rats.

scholarly journals Atrial arrhythmias and autonomic dysfunction in rats exposed to chronic intermittent hypoxia

2018 ◽  
Vol 314 (6) ◽  
pp. H1160-H1168 ◽  
Author(s):  
Sara L. Bober ◽  
John Ciriello ◽  
Douglas L. Jones
Keyword(s):  
Obstructive Sleep Apnea ◽  
Electrical Stimulation ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Receptor Protein ◽  
Chronic Intermittent Hypoxia ◽  
Programmed Electrical Stimulation ◽  
Protein Levels ◽  
Obstructive Sleep ◽  
Atrial Vulnerability

Obstructive sleep apnea, which involves chronic intermittent hypoxia (CIH), is a major risk factor for developing atrial fibrillation (AF). Whether or not CIH alone alters cardiac mechanisms to support AF is unknown. This study investigated the effects of CIH on atrial electrophysiology and arrhythmia vulnerability and evaluated the role of autonomics in CIH promotion of AF. Adult male Sprague-Dawley rats were exposed to 8 h/day of CIH or normoxia for 7 days. After exposure, rats were anesthetized for intracardiac electrophysiological experiments. Atrial effective refractory periods (AERPs) and AF inducibility were determined using programmed electrical stimulation and burst pacing in the absence and presence of autonomic receptor agonists and antagonists. Western blot analysis measured atrial protein expression of muscarinic M2, M3, and β1-adrenergic receptors. Compared with normoxia-exposed control rats, CIH-exposed rats had enhanced AF vulnerability using both programmed electrical stimulation and burst pacing, accompanied by greater AERP responses to carbachol and propranolol, lesser responses to isoproterenol, and higher atrial M2 receptor protein levels. Enhanced atrial vulnerability was accentuated by carbachol and abolished by atropine, indicating that the AF-promoting effects of CIH depended principally on parasympathetic activation. Enhancement of atrial vulnerability and AERP shortening with cholinergic agonists in CIH-exposed rats is consistent with sensitivity to parasympathetic activation. Higher responses to adrenergic receptor blockade in CIH-exposed rats is consistent with sympathetic potentiation. These findings implicate CIH as an important mediator of enhanced AF susceptibility in obstructive sleep apnea and provide novel insights into the underlying mechanisms. NEW & NOTEWORTHY Our study demonstrates, for the first time, that chronic intermittent hypoxia alone enhances vulnerability to atrial arrhythmia induction, which depends principally on parasympathetic activation. Enhanced atrial vulnerability was accompanied by heightened electrophysiological responses of the atrial myocardium to carbachol and isoproterenol, dampened responses to propranolol, and increased atrial M2 receptor protein levels.

scholarly journals Caspase lesions of PVN-projecting MnPO neurons block the sustained component of CIH-induced hypertension in adult male rats

2020 ◽  
Vol 318 (1) ◽  
pp. H34-H48
Author(s):  
Alexandria B. Marciante ◽  
Lei A. Wang ◽  
Joel T. Little ◽  
J. Thomas Cunningham
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Chronic Hypertension ◽  
Pressure Regulation ◽  
Neurogenic Hypertension ◽  
Obstructive Sleep ◽  
Induced Hypertension

Obstructive sleep apnea is characterized by interrupted breathing that leads to cardiovascular sequelae including chronic hypertension that can persist into the waking hours. Chronic intermittent hypoxia (CIH), which models the hypoxemia associated with sleep apnea, is sufficient to cause a sustained increase in blood pressure that involves the central nervous system. The median preoptic nucleus (MnPO) is an integrative forebrain region that contributes to blood pressure regulation and neurogenic hypertension. The MnPO projects to the paraventricular nucleus (PVN), a preautonomic region. We hypothesized that pathway-specific lesions of the projection from the MnPO to the PVN would attenuate the sustained component of chronic intermittent hypoxia-induced hypertension. Adult male Sprague-Dawley rats (250–300 g) were anesthetized with isoflurane and stereotaxically injected bilaterally in the PVN with a retrograde Cre-containing adeno-associated virus (AAV; AAV9.CMV.HI.eGFP-Cre.WPRE.SV40) and injected in the MnPO with caspase-3 (AAV5-flex-taCasp3-TEVp) or control virus (AAV5-hSyn-DIO-mCherry). Three weeks after the injections the rats were exposed to a 7-day intermittent hypoxia protocol. During chronic intermittent hypoxia, controls developed a diurnal hypertension that was blunted in rats with caspase lesions. Brain tissue processed for FosB immunohistochemistry showed decreased staining with caspase-induced lesions of MnPO and downstream autonomic-regulating nuclei. Chronic intermittent hypoxia significantly increased plasma levels of advanced oxidative protein products in controls, but this increase was blocked in caspase-lesioned rats. The results indicate that PVN-projecting MnPO neurons play a significant role in blood pressure regulation in the development of persistent chronic intermittent hypoxia hypertension. NEW & NOTEWORTHY Chronic intermittent hypoxia associated with obstructive sleep apnea increases oxidative stress and leads to chronic hypertension. Sustained hypertension may be mediated by angiotensin II-induced neural plasticity of excitatory median preoptic neurons in the forebrain that project to the paraventricular nucleus of the hypothalamus. Selective caspase lesions of these neurons interrupt the drive for sustained hypertension and cause a reduction in circulating oxidative protein products. This indicates that a functional connection between the forebrain and hypothalamus is necessary to drive diurnal hypertension associated with intermittent hypoxia. These results provide new information about central mechanisms that may contribute to neurogenic hypertension.

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