scholarly journals Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model

2020 ◽  
Vol 21 (14) ◽  
pp. 4893 ◽  
Author(s):  
Elena Olea ◽  
Inmaculada Docio ◽  
Miguel Quintero ◽  
Asunción Rocher ◽  
Ana Obeso ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Intermittent Hypoxia ◽  
Secretory Activity ◽  
Whole Body ◽  
Chronic Intermittent Hypoxia ◽  
Antiemetic Drug ◽  
Therapeutic Opportunity ◽  
Dopamine 2 Receptor ◽  
Hypopnea Syndrome ◽  
Analogous Effect

The sleep apnea-hypopnea syndrome (SAHS) involves periods of intermittent hypoxia, experimentally reproduced by exposing animal models to oscillatory PO2 patterns. In both situations, chronic intermittent hypoxia (CIH) exposure produces carotid body (CB) hyperactivation generating an increased input to the brainstem which originates sympathetic hyperactivity, followed by hypertension that is abolished by CB denervation. CB has dopamine (DA) receptors in chemoreceptor cells acting as DA-2 autoreceptors. The aim was to check if blocking DA-2 receptors could decrease the CB hypersensitivity produced by CIH, minimizing CIH-related effects. Domperidone (DOM), a selective peripheral DA-2 receptor antagonist that does not cross the blood-brain barrier, was used to examine its effect on CIH (30 days) exposed rats. Arterial pressure, CB secretory activity and whole-body plethysmography were measured. DOM, acute or chronically administered during the last 15 days of CIH, reversed the hypertension produced by CIH, an analogous effect to that obtained with CB denervation. DOM marginally decreased blood pressure in control animals and did not affect hypoxic ventilatory response in control or CIH animals. No adverse effects were observed. DOM, used as gastrokinetic and antiemetic drug, could be a therapeutic opportunity for hypertension in SAHS patients’ resistant to standard treatments.

Impact of histaminergic H3 receptor antagonist on hypoglossal nucleus in chronic intermittent hypoxia conditions

2020 ◽  
Vol 238 (1) ◽  
pp. 121-131
Author(s):  
Liang Xie ◽  
Qinhan Wu ◽  
Weiping Hu ◽  
Xu Wu ◽  
Guiling Xiang ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Intermittent Hypoxia ◽  
Hypoglossal Nucleus ◽  
Chronic Intermittent Hypoxia ◽  
H3 Receptor

scholarly journals Chronic Intermittent Hypoxia Impairs Insulin Sensitivity but Improves Whole-Body Glucose Tolerance by Activating Skeletal Muscle AMPK

Diabetes ◽  
2017 ◽  
Vol 66 (12) ◽  
pp. 2942-2951 ◽  
Author(s):  
Amandine Thomas ◽  
Elise Belaidi ◽  
Sophie Moulin ◽  
Sandrine Horman ◽  
Gerard C. van der Zon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Intermittent Hypoxia ◽  
Whole Body ◽  
Chronic Intermittent Hypoxia

Chronic intermittent hypoxia reduces ventilatory long-term facilitation and enhances apnea frequency in newborn rats

2008 ◽  
Vol 294 (4) ◽  
pp. R1356-R1366 ◽  
Author(s):  
Cécile Julien ◽  
Aida Bairam ◽  
Vincent Joseph
Keyword(s):  
Intermittent Hypoxia ◽  
Gradual Increase ◽  
Minute Ventilation ◽  
Whole Body ◽  
Male Rat ◽  
Chronic Intermittent Hypoxia ◽  
Protective Mechanism ◽  
Rat Pups ◽  
Long Term Facilitation

Ventilatory long-term facilitation (LTF; defined as gradual increase of minute ventilation following repeated hypoxic exposures) is well described in adult mammals and is hypothesized to be a protective mechanism against apnea. In newborns, LTF is absent during the first postnatal days, but its precise developmental pattern is unknown. Accordingly, this study describes this pattern of postnatal development. Additionally, we tested the hypothesis that chronic intermittent hypoxia (CIH) from birth alters this development. LTF was estimated in vivo using whole body plethysmography by exposing rat pups at postnatal days 1, 4, and 10 (P1, P4, and P10) to 10 brief hypoxic cycles (nadir 5% O2) and respiratory recordings during the following 2 h (recovery, 21% O2). Under these conditions, ventilatory LTF (gradual increase of minute ventilation during recovery) was clearly expressed in P10 rats but not in P1 and P4. In a second series of experiments, rat pups were exposed to CIH during the first 10 postnatal days (6 brief cyclic exposures at 5% O2 every 6 min followed by 1 h under normoxia, 24 h a day). Compared with P10 control rats, CIH enhanced hypoxic ventilatory response (estimated during the hypoxic cycles) specifically in male rat pups. Ventilatory LTF was drastically reduced in P10 rats exposed to CIH, which was associated with higher apnea frequency during recovery. We conclude that CIH from birth enhances hypoxic chemoreflex and disrupts LTF development, thus likely contributing to increase apnea frequency.

scholarly journals Role of Raphe Magnus 5-HT1A Receptor in Increased Ventilatory Responses Induced by Intermittent Hypoxia in Rats

2021 ◽  
Author(s):  
Jiao Su ◽  
Yang Meng ◽  
Yifei Fang ◽  
Linge Sun ◽  
Mengge Wang ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Male Rats ◽  
Whole Body ◽  
Chronic Intermittent Hypoxia ◽  
Control Group ◽  
Dependent Manner ◽  
Ventilatory Responses ◽  
Hypoxia Group ◽  
Raphe Magnus ◽  
Experimental Group

Abstract Background: Intermittent hypoxia induces increased ventilatory responses in a 5-HT-dependent manner. This study aimed to explore that effect of raphe magnus serotonin 1A receptor (5-HT1A) receptor on the increased ventilatory responses induced by intermittent hypoxia.Methods: Stereotaxic surgery was performed in adult male rats, and acute and chronic intermittent hypoxia models were established after recovery from surgery. The experimental group received microinjections of 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the raphe magnus nucleus (RMg). Meanwhile, the control group received microinjections of artificial cerebrospinal fluid instead of 8-OH-DPAT. Whole-body plethysmography was performed, and ventilatory responses were compared among the different groups of oxygen status.Results: Compared with the normoxia group, the acute intermittent hypoxia group exhibited higher ventilatory responses (e.g., shorter inspiratory time and higher tidal volume, frequency of breathing, minute ventilation, and mean inspiratory flow) (P<0.05). 8-OH-DPAT microinjection partly weakened these changes in the acute intermittent hypoxia group. Further, compared with the acute intermittent hypoxia group, rats in chronic intermittent hypoxia group exhibited higher measures of ventilatory responses after 1 day of intermittent hypoxia (P<0.05). These effects peaked after 3 days of intermittent hypoxia treatment and then decreased gradually. Moreover, these changes were diminished and even disappeared in the experimental group.Conclusions: The results indicate that RMg 5-HT1A receptor is involved in the modulation of the increased ventilatory responses induced by intermittent hypoxia.

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 Roles and Mechanisms of Obstructive Sleep Apnea-Hypopnea Syndrome and Chronic Intermittent Hypoxia in Atherosclerosis: Evidence and Prospective

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Linqin Ma ◽  
Jingchun Zhang ◽  
Yue Liu
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Underlying Mechanism ◽  
Endothelial Injury ◽  
Current Evidence ◽  
Chronic Intermittent Hypoxia ◽  
Vascular Endothelial ◽  
Obstructive Sleep ◽  
Hypopnea Syndrome

The morbidity and mortality of obstructive sleep apnea-hypopnea syndrome (OSAHS) are regarded as consequences of its adverse effects on the cardiovascular system. Chronic intermittent hypoxia (CIH) induced by OSAHS can result in vascular endothelial injury, thus promoting development of atherosclerosis (AS). Studies have shown that CIH is an independent risk factor for the occurrence and development of AS, but the underlying mechanism remains unclear. Here, we review clinical and fundamental studies reported during the last 10 years on the occurrence and development of AS mediated by CIH, focusing on inflammation, oxidative stress, insulin resistance, cell apoptosis, vascular endothelial injury, platelet activation, and neuroendocrine disorders. This review will offer current evidence and perspective to researchers for the development of effective intervention strategies for OSAHS-related cardiocerebrovascular diseases.

scholarly journals Carotid body denervation prevents fasting hyperglycemia during chronic intermittent hypoxia

2014 ◽  
Vol 117 (7) ◽  
pp. 765-776 ◽  
Author(s):  
Mi-Kyung Shin ◽  
Qiaoling Yao ◽  
Jonathan C. Jun ◽  
Shannon Bevans-Fonti ◽  
Doo-Young Yoo ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Fasting Blood Glucose ◽  
Whole Body ◽  
Chronic Intermittent Hypoxia ◽  
Glucose Flux ◽  
Obstructive Sleep ◽  
Glucose Output ◽  
Carotid Body Denervation

Obstructive sleep apnea causes chronic intermittent hypoxia (IH) and is associated with impaired glucose metabolism, but mechanisms are unknown. Carotid bodies orchestrate physiological responses to hypoxemia by activating the sympathetic nervous system. Therefore, we hypothesized that carotid body denervation would abolish glucose intolerance and insulin resistance induced by chronic IH. Male C57BL/6J mice underwent carotid sinus nerve dissection (CSND) or sham surgery and then were exposed to IH or intermittent air (IA) for 4 or 6 wk. Hypoxia was administered by decreasing a fraction of inspired oxygen from 20.9% to 6.5% once per minute, during the 12-h light phase (9 a.m.–9 p.m.). As expected, denervated mice exhibited blunted hypoxic ventilatory responses. In sham-operated mice, IH increased fasting blood glucose, baseline hepatic glucose output (HGO), and expression of a rate-liming hepatic enzyme of gluconeogenesis phospho enolpyruvate carboxykinase (PEPCK), whereas the whole body glucose flux during hyperinsulinemic euglycemic clamp was not changed. IH did not affect glucose tolerance after adjustment for fasting hyperglycemia in the intraperitoneal glucose tolerance test. CSND prevented IH-induced fasting hyperglycemia and increases in baseline HGO and liver PEPCK expression. CSND trended to augment the insulin-stimulated glucose flux and enhanced liver Akt phosphorylation at both hypoxic and normoxic conditions. IH increased serum epinephrine levels and liver sympathetic innervation, and both increases were abolished by CSND. We conclude that chronic IH induces fasting hyperglycemia increasing baseline HGO via the CSN sympathetic output from carotid body chemoreceptors, but does not significantly impair whole body insulin sensitivity.

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