Role of oxidative stress-induced endothelin-converting enzyme activity in the alteration of carotid body function by chronic intermittent hypoxia

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.

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

Journal of Histochemistry & Cytochemistry ◽

10.1369/0022155418776229 ◽

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.

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Genistein attenuates genioglossus muscle fatigue under chronic intermittent hypoxia by down-regulation of oxidative stress level and up-regulation of antioxidant enzyme activity through ERK1/2 signaling pathway

Oral Diseases ◽

10.1111/j.1601-0825.2011.01822.x ◽

2011 ◽

Vol 17 (7) ◽

pp. 677-684 ◽

Cited By ~ 18

Author(s):

WH Ding ◽

YH Liu

Keyword(s):

Oxidative Stress ◽

Enzyme Activity ◽

Muscle Fatigue ◽

Antioxidant Enzyme ◽

Signaling Pathway ◽

Intermittent Hypoxia ◽

Antioxidant Enzyme Activity ◽

Chronic Intermittent Hypoxia ◽

Genioglossus Muscle ◽

Oxidative Stress Level

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Role of Endothelin-1 on the Enhanced Carotid Body Activity Induced by Chronic Intermittent Hypoxia

THE ARTERIAL CHEMORECEPTORS - ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY ◽

10.1007/0-387-31311-7_53 ◽

2006 ◽

pp. 345-350 ◽

Cited By ~ 4

Author(s):

SERGIO REY ◽

RODRIGO DEL RIO ◽

RODRIGO ITURRIAGA

Keyword(s):

Carotid Body ◽

Intermittent Hypoxia ◽

Chronic Intermittent Hypoxia ◽

Endothelin 1 ◽

Body Activity

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

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfw158.09 ◽

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

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00472.2016 ◽

2017 ◽

Vol 312 (2) ◽

pp. R245-R252 ◽

Cited By ~ 4

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.

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Chronic intermittent hypoxia-induced vascular enlargement and VEGF upregulation in the rat carotid body is not prevented by antioxidant treatment

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00128.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. L702-L711 ◽

Cited By ~ 24

Author(s):

Rodrigo Del Rio ◽

Cristian Muñoz ◽

Paulina Arias ◽

Felipe A. Court ◽

Esteban A. Moya ◽

...

Keyword(s):

Oxidative Stress ◽

Ascorbic Acid ◽

Carotid Body ◽

Intermittent Hypoxia ◽

Vessel Diameter ◽

Chronic Intermittent Hypoxia ◽

Sprague Dawley ◽

Antioxidant Treatment ◽

Sprague Dawley Rats ◽

Vascular Area

Chronic intermittent hypoxia (CIH), a characteristic of sleep obstructive apnea, enhances carotid body (CB) chemosensory responses to hypoxia, but its consequences on CB vascular area and VEGF expression are unknown. Accordingly, we studied the effect of CIH on CB volume, glomus cell numbers, blood vessel diameter and number, and VEGF immunoreactivity (VEGF-ir) in male Sprague-Dawley rats exposed to 5% O2, 12 times/h for 8 h or sham condition for 21 days. We found that CIH did not modify the CB volume or the number of glomus cells but increased VEGF-ir and enlarged the vascular area by increasing the size of the blood vessels, whereas the number of the vessels was unchanged. Because oxidative stress plays an essential role in the CIH-induced carotid chemosensory potentiation, we tested whether antioxidant treatment with ascorbic acid may impede the vascular enlargement and the VEGF upregulation. Ascorbic acid, which prevents the CB chemosensory potentiation, failed to impede the vascular enlargement and the increased VEGF-ir. Thus present results suggest that the CB vascular enlargement induced by CIH is a direct effect of intermittent hypoxia and not secondary to the oxidative stress. Accordingly, the subsequent capillary changes may be secondary to the mechanisms involved in the neural chemosensory plasticity induced by intermittent hypoxia.

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