scholarly journals Cardiac Response to Chronic Intermittent Hypoxia with a Transition from Adaptation to Maladaptation:The Role of Hydrogen Peroxide

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Xia Yin ◽  
Yang Zheng ◽  
Quan Liu ◽  
Jun Cai ◽  
Lu Cai
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Intermittent Hypoxia ◽  
Cardiac Response ◽  
Chronic Intermittent Hypoxia ◽  
Critical Element ◽  
Respiratory Disorder ◽  
Obstructive Sleep ◽  
Antioxidative Therapy

Obstructive sleep apnea (OSA) is a highly prevalent respiratory disorder of sleep, and associated with chronic intermittent hypoxia (CIH). Experimental evidence indicates that CIH is a unique physiological state with potentially “adaptive” and “maladaptive” consequences for cardio-respiratory homeostasis. CIH is also a critical element accounting for most of cardiovascular complications of OSA. Cardiac response to CIH is time-dependent, showing a transition from cardiac compensative (such as hypertrophy) to decompensating changes (such as failure). CIH-provoked mild and transient oxidative stress can induce adaptation, but severe and persistent oxidative stress may provoke maladaptation. Hydrogen peroxide as one of major reactive oxygen species plays an important role in the transition of adaptive to maladaptive response to OSA-associated CIH. This may account for the fact that although oxidative stress has been recognized as a driver of cardiac disease progression, clinical interventions with antioxidants have had little or no impact on heart disease and progression. Here we focus on the role of hydrogen peroxide in CIH and OSA, trying to outline the potential of antioxidative therapy in preventing CIH-induced cardiac damage.

scholarly journals Curcumin prevents chronic intermittent hypoxia-induced myocardial injury

2020 ◽  
Vol 11 ◽  
pp. 204062232092210 ◽  
Author(s):  
Sophie Moulin ◽  
Claire Arnaud ◽  
Sophie Bouyon ◽  
Jean-Louis Pépin ◽  
Diane Godin-Ribuot ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Er Stress ◽  
Intermittent Hypoxia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Sleep Apnoea ◽  
Cardiac Response ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep

Background: Chronic intermittent hypoxia (IH), the hallmark feature of obstructive sleep apnoea syndrome, contributes to infarct size enhancement after myocardial ischemia–reperfusion (I/R). Curcumin (Curc), the natural pigment of Curcuma longa, has been demonstrated to be beneficial in the context of myocardial injury. In this study, we assessed the effects of Curc on the maladaptive cardiac response to IH, and particularly on IH-induced hypoxia inducible factor-1 (HIF-1) expression, oxidative stress, inflammation, endoplasmic reticulum (ER) stress and apoptosis. Methods: Swiss/SV129 mice were exposed to normoxia or IH (21–5% FiO2, 60 s cycles, 8 h per day, for 21 days) and treated orally with Curc (100 mg kg−1 day−1, oral gavage) or its vehicle. Mice were then either euthanised for heart sampling in order to perform biochemical and histological analysis, or subjected to an in vivo ischemia-reperfusion protocol in order to measure infarct size. Results: IH increased nuclear HIF-1α expression and superoxide anion (O2.–) production as well as nuclear factor kappa B (NF-kB) p65, glucose-regulated protein (Grp78) and C/EBP homologous protein (CHOP) expression. IH also induced apoptosis and increased infarct size after I/R . The IH-induced HIF-1 activation, oxidative stress, inflammation, ER stress and apoptosis were abolished by chronic Curc treatment. Curc also significantly decreased infarct size only in mice exposed to IH. Conclusion: Curc prevents IH-induced myocardial cell death signalling. Curc might be used as a combined therapy with continuous positive airway pressure in sleep apnoea patients with high cardiovascular risk.

scholarly journals Intermittent Hypoxia Increases the Severity of Bleomycin-Induced Lung Injury in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Thomas Gille ◽  
Morgane Didier ◽  
Cécile Rotenberg ◽  
Eva Delbrel ◽  
Dominique Marchant ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Fibrosis ◽  
Pulmonary Edema ◽  
Cell Apoptosis ◽  
Lung Fibrosis ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep ◽  
The Impact ◽  
Lung Oxidative Stress

Background. Severe obstructive sleep apnea (OSA) with chronic intermittent hypoxia (IH) is common in idiopathic pulmonary fibrosis (IPF). Here, we evaluated the impact of IH on bleomycin- (BLM-) induced pulmonary fibrosis in mice. Methods. C57BL/6J mice received intratracheal BLM or saline and were exposed to IH (40 cycles/hour; FiO2 nadir: 6%; 8 hours/day) or intermittent air (IA). In the four experimental groups, we evaluated (i) survival; (ii) alveolar inflammation, pulmonary edema, lung oxidative stress, and antioxidant enzymes; (iii) lung cell apoptosis; and (iv) pulmonary fibrosis. Results. Survival at day 21 was lower in the BLM-IH group (p<0.05). Pulmonary fibrosis was more severe at day 21 in BLM-IH mice, as assessed by lung collagen content (p=0.02) and histology. At day 4, BLM-IH mice developed a more severe neutrophilic alveolitis, (p<0.001). Lung oxidative stress was observed, and superoxide dismutase and glutathione peroxidase expression was decreased in BLM-IH mice (p<0.05 versus BLM-IA group). At day 8, pulmonary edema was observed and lung cell apoptosis was increased in the BLM-IH group. Conclusion. These results show that exposure to chronic IH increases mortality, lung inflammation, and lung fibrosis in BLM-treated mice. This study raises the question of the worsening impact of severe OSA in IPF patients.

scholarly journals Maladaptive Pulmonary Vascular Responses to Chronic Sustained and Chronic Intermittent Hypoxia in Rat

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 54
Author(s):  
Jesus Prieto-Lloret ◽  
Elena Olea ◽  
Ana Gordillo-Cano ◽  
Inmaculada Docio ◽  
Ana Obeso ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Carotid Body ◽  
Pulmonary Circulation ◽  
Intermittent Hypoxia ◽  
Pulmonary Arteries ◽  
Systemic Circulation ◽  
Systemic Hypertension ◽  
Chronic Intermittent Hypoxia ◽  
Respiratory Disorder ◽  
Obstructive Sleep

Chronic sustained hypoxia (CSH), as found in individuals living at a high altitude or in patients suffering respiratory disorders, initiates physiological adaptations such as carotid body stimulation to maintain oxygen levels, but has deleterious effects such as pulmonary hypertension (PH). Obstructive sleep apnea (OSA), a respiratory disorder of increasing prevalence, is characterized by a situation of chronic intermittent hypoxia (CIH). OSA is associated with the development of systemic hypertension and cardiovascular pathologies, due to carotid body and sympathetic overactivation. There is growing evidence that CIH can also compromise the pulmonary circulation, causing pulmonary hypertension in OSA patients and animal models. The aim of this work was to compare hemodynamics, vascular contractility, and L-arginine-NO metabolism in two models of PH in rats, associated with CSH and CIH exposure. We demonstrate that whereas CSH and CIH cause several common effects such as an increased hematocrit, weight loss, and an increase in pulmonary artery pressure (PAP), compared to CIH, CSH seems to have more of an effect on the pulmonary circulation, whereas the effects of CIH are apparently more targeted on the systemic circulation. The results suggest that the endothelial dysfunction evident in pulmonary arteries with both hypoxia protocols are not due to an increase in methylated arginines in these arteries, although an increase in plasma SDMA could contribute to the apparent loss of basal NO-dependent vasodilation and, therefore, the increase in PAP that results from CIH.

scholarly journals Nitration of MnSOD in the Carotid Body and Adrenal Gland Induced by Chronic Intermittent Hypoxia

2018 ◽  
Vol 66 (10) ◽  
pp. 753-765
Author(s):  
Esteban A. Moya ◽  
Paulina Arias ◽  
Rodrigo Iturriaga
Keyword(s):  
Oxidative Stress ◽  
Adrenal Gland ◽  
Enzymatic Activity ◽  
Adrenal Medulla ◽  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Sprague Dawley ◽  
Obstructive Sleep ◽  
Key Enzyme

Chronic intermittent hypoxia (CIH), main feature of obstructive sleep apnea, produces nitro-oxidative stress, which contributes to potentiate carotid body (CB) chemosensory discharges and sympathetic-adrenal-axis activity, leading to hypertension. The MnSOD enzymatic activity, a key enzyme on oxidative stress control, is reduced by superoxide-induced nitration. However, the effects of CIH-induced nitration on MnSOD enzymatic activity in the CB and adrenal gland are not known. We studied the effects of CIH on MnSOD protein and immunoreactive (MnSOD-ir) levels in the CB, adrenal gland and superior cervical ganglion (SCG), and on 3-nitrotyrosine (3-NT-ir), CuZnSOD (CuZnSOD-ir), MnSOD nitration, and its enzymatic activity in the CB and adrenal gland from male Sprague-Dawley rats exposed to CIH for 7 days. CIH increased 3-NT-ir in CB and adrenal gland, whereas MnSOD-ir increased in the CB and in adrenal cortex, but not in the whole adrenal medulla or SCG. CIH nitrated MnSOD in the CB and adrenal medulla, but its activity decreased in the adrenal gland. CuZnSOD-ir remained unchanged in both tissues. All changes observed were prevented by ascorbic acid treatment. Present results show that CIH for 7 days produced MnSOD nitration, but failed to reduce its activity in the CB, because of the increased protein level.

scholarly journals Chronic Intermittent Hypoxia Induces Early-Stage Metabolic Dysfunction Independently of Adipose Tissue Deregulation

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1233
Author(s):  
Fátima O. Martins ◽  
Joana F. Sacramento ◽  
Elena Olea ◽  
Bernardete F. Melo ◽  
Jesus Prieto-Lloret ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Intermittent Hypoxia ◽  
Early Stage ◽  
Tissue Hypoxia ◽  
Whole Body ◽  
Chronic Intermittent Hypoxia ◽  
Adipose Tissue Dysfunction ◽  
Obstructive Sleep

Several studies demonstrated a link between obstructive sleep apnea (OSA) and the development of insulin resistance. However, the main event triggering insulin resistance in OSA remains to be clarified. Herein, we investigated the effect of mild and severe chronic intermittent hypoxia (CIH) on whole-body metabolic deregulation and visceral adipose tissue dysfunction. Moreover, we studied the contribution of obesity to CIH-induced dysmetabolic states. Experiments were performed in male Wistar rats submitted to a control and high-fat (HF) diet. Two CIH protocols were tested: A mild CIH paradigm (5/6 hypoxic (5% O2) cycles/h, 10.5 h/day) during 35 days and a severe CIH paradigm (30 hypoxic (5% O2) cycles, 8 h/day) during 15 days. Fasting glycemia, insulinemia, insulin sensitivity, weight, and fat mass were assessed. Adipose tissue hypoxia, inflammation, angiogenesis, oxidative stress, and metabolism were investigated. Mild and severe CIH increased insulin levels and induced whole-body insulin resistance in control animals, effects not associated with weight gain. In control animals, CIH did not modify adipocytes perimeter as well as adipose tissue hypoxia, angiogenesis, inflammation or oxidative stress. In HF animals, severe CIH attenuated the increase in adipocytes perimeter, adipose tissue hypoxia, angiogenesis, and dysmetabolism. In conclusion, adipose tissue dysfunction is not the main trigger for initial dysmetabolism in CIH. CIH in an early stage might have a protective role against the deleterious effects of HF diet on adipose tissue metabolism.

scholarly journals SP081PATHOPHYSIOLOGICAL ROLE OF KIDNEY IN SYSTEMIC OXIDATIVE STRESS DURING CHRONIC INTERMITTENT HYPOXIA

2016 ◽  
Vol 31 (suppl_1) ◽  
pp. i112-i113
Author(s):  
Keiko Takahashi ◽  
Takashi Kobayashi ◽  
Takeshi Sugaya ◽  
Akira Nishiyama ◽  
Yoshihide Fujisawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Systemic Oxidative Stress

scholarly journals Role of angiotensin-converting enzyme 1 within the median preoptic nucleus following chronic intermittent hypoxia

2017 ◽  
Vol 312 (2) ◽  
pp. R245-R252 ◽  
Author(s):  
Katelynn Faulk ◽  
Brent Shell ◽  
T. Prashant Nedungadi ◽  
J. Thomas Cunningham
Keyword(s):  
Blood Pressure ◽  
Sleep Apnea ◽  
Angiotensin Converting Enzyme ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Converting Enzyme ◽  
Preoptic Nucleus ◽  
Median Preoptic Nucleus ◽  
Obstructive Sleep

Sustained hypertension is an important consequence of obstructive sleep apnea. An animal model of the hypoxemia associated with sleep apnea, chronic intermittent hypoxia (CIH), produces increased sympathetic nerve activity (SNA) and sustained increases in blood pressure. Many mechanisms have been implicated in the hypertension associated with CIH, including the role of ΔFosB within the median preoptic nucleus (MnPO). Also, the renin-angiotensin system (RAS) has been associated with CIH hypertension. We conducted experiments to determine the possible association of FosB/ΔFosB with a RAS component, angiotensin-converting enzyme 1 (ACE1), within the MnPO following 7 days of CIH. Retrograde tract tracing from the paraventricular nucleus (PVN), a downstream region of the MnPO, was used to establish a potential pathway for FosB/ΔFosB activation of MnPO ACE1 neurons. After CIH, ACE1 cells with FosB/ΔFosB expression increased colocalization with a retrograde tracer that was injected unilaterally within the PVN. Also, Western blot examination showed ACE1 protein expression increasing within the MnPO following CIH. Chromatin immunoprecipitation (ChIP) assays demonstrated an increase in FosB/ΔFosB association with the ACE1 gene within the MnPO following CIH. FosB/ΔFosB may transcriptionally target ACE1 within the MnPO following CIH to affect the downstream PVN region, which may influence SNA and blood pressure.

scholarly journals Cardiovascular Complications of Sleep Apnea: Role of Oxidative Stress

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Mohammad Badran ◽  
Najib Ayas ◽  
Ismail Laher
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Animal Models ◽  
Intermittent Hypoxia ◽  
Cardiovascular Complications ◽  
Middle Aged ◽  
Cellular Mechanisms ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) occurs in 2% of middle-aged women and 4% of middle-aged men with a higher prevalence among obese subjects. This condition is considered as an independent risk factor for cerebrovascular and cardiovascular diseases. One of the major pathophysiological characteristics of OSA is intermittent hypoxia. Hypoxia can lead to oxidative stress and overproduction of reactive oxygen species, which can lead to endothelial dysfunction, a hallmark of atherosclerosis. Many animal models, such as the rodent model of intermittent hypoxia, mimic obstructive sleep apnea in human patients and allow more in-depth investigation of biological and cellular mechanisms of this condition. This review discusses the role of oxidative stress in cardiovascular disease resulting from OSA in humans and animal models.

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