scholarly journals Neural regulation of hypoxia-inducible factors and redox state drives the pathogenesis of hypertension in a rodent model of sleep apnea

2015 ◽  
Vol 119 (10) ◽  
pp. 1152-1156 ◽  
Author(s):  
Gregg L. Semenza ◽  
Nanduri R. Prabhakar
Keyword(s):  
Nervous System ◽  
Sleep Apnea ◽  
Sympathetic Nervous System ◽  
Brain Stem ◽  
Carotid Body ◽  
Sympathetic Neurons ◽  
Ventrolateral Medulla ◽  
Obstructive Sleep ◽  
Sympathetic Nervous ◽  
The Brain

Obstructive sleep apnea (OSA) is one of the most common causes of hypertension in western societies. OSA causes chronic intermittent hypoxia (CIH) in specialized O2-sensing glomus cells of the carotid body. CIH generates increased reactive oxygen species (ROS) that trigger a feedforward mechanism in which increased intracellular calcium levels ([Ca2+]i) trigger increased HIF-1α synthesis and increased HIF-2α degradation. As a result, the normal homeostatic balance between HIF-1α-dependent prooxidant and HIF-2α-dependent antioxidant enzymes is disrupted, leading to further increases in ROS. Carotid body sensory nerves project to the nucleus tractus solitarii, from which the information is relayed via interneurons to the rostral ventrolateral medulla in the brain stem, which sends sympathetic neurons to the adrenal medulla to stimulate the release of epinephrine and norepinephrine, catecholamines that increase blood pressure. At each synapse, neurotransmitters trigger increased [Ca2+]i, HIF-1α:HIF-2α, and Nox2:Sod2 activity that generates increased ROS levels. These responses are not observed in other regions of the brain stem that do not receive input from the carotid body or signal to the sympathetic nervous system. Thus sympathetic nervous system homeostasis is dependent on a balance between HIF-1α and HIF-2α, disruption of which results in hypertension in OSA patients.

Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension

2011 ◽  
Vol 300 (4) ◽  
pp. R818-R826 ◽  
Author(s):  
Yoshitaka Hirooka ◽  
Takuya Kishi ◽  
Koji Sakai ◽  
Akira Takeshita ◽  
Kenji Sunagawa
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Brain Stem ◽  
Intracellular Signaling ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Sympathetic Nervous ◽  
The Brain

Nitric oxide (NO) and reactive oxygen species (ROS) play important roles in blood pressure regulation via the modulation of the autonomic nervous system, particularly in the central nervous system (CNS). In general, accumulating evidence suggests that NO inhibits, but ROS activates, the sympathetic nervous system. NO and ROS, however, interact with each other. Our consecutive studies and those of others strongly indicate that an imbalance between NO bioavailability and ROS generation in the CNS, including the brain stem, activates the sympathetic nervous system, and this mechanism is involved in the pathogenesis of neurogenic aspects of hypertension. In this review, we focus on the role of NO and ROS in the regulation of the sympathetic nervous system within the brain stem and subsequent cardiovascular control. Multiple mechanisms are proposed, including modulation of neurotransmitter release, inhibition of receptors, and alterations of intracellular signaling pathways. Together, the evidence indicates that an imbalance of NO and ROS in the CNS plays a pivotal role in the pathogenesis of hypertension.

scholarly journals Sympathetic nervous system and serum leptin level in obese patients with and without obstructive sleep apnea

2006 ◽  
Vol 12 (3) ◽  
pp. 256-261
Author(s):  
N. E. Zvartau ◽  
Yu. V. Sviryaev ◽  
O. P. Rotari ◽  
I. V. Emelyanov ◽  
N. K. Merculova ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Nervous System ◽  
Sleep Apnea ◽  
Sympathetic Nervous System ◽  
Sympathetic Activity ◽  
Obese Patients ◽  
Serum Leptin ◽  
Nervous System Activity ◽  
Obstructive Sleep ◽  
Sympathetic Nervous

The aim of the present study was to investigate sympathetic nervous system activity and serum leptin level in obese patients with and without obstructive sleep apnea (OSA). We examined 75 OSA patients and 40 age, weight, BMI and blood pressure levels matched obese patients without OSA. As a result, patients with OSA had higher sympathetic activity associated not only with repetitive episodes of hypoxia/hypercapnia during sleep, but also with more marked central obesity and higher serum leptin level.

scholarly journals The Assessment of Endothelial Dysfunction among OSA Patients after CPAP Treatment

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 310
Author(s):  
Klaudia Brożyna-Tkaczyk ◽  
Wojciech Myśliński ◽  
Jerzy Mosiewicz
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Obstructive Sleep Apnea ◽  
Nervous System ◽  
Sleep Apnea ◽  
Endothelial Dysfunction ◽  
Sympathetic Nervous System ◽  
Cpap Treatment ◽  
Obstructive Sleep ◽  
Sympathetic Nervous

Background and Objectives: Microcirculation dysfunction is present in patients with obstructive sleep apnea (OSA). Intermittent hypoxia generates “oxidative stress”, which contributes to chronic inflammation. The secretion of nitric oxide (NO), which is responsible for adequate regulation of the endothelium, is impaired due to a decrease in endothelial nitric oxide synthetase (eNOS) expression and an increase in endogenous eNOS inhibitors. Furthermore, nocturnal awakenings lead to the dysregulation of cortisol release and increased stimulation of the sympathetic nervous system. The non-invasive method of choice in OSA treatment is continuous positive airway pressure (CPAP). Materials and Methods: PubMed, Scopus, and Google Scholar databases were searched, and only papers published in the last 15 years were subsequently analyzed. For this purpose, we searched for keywords in article titles or contents such as “obstructive sleep apnea”, “microcirculation”, and “CPAP”. In our review, we only studied English articles that reported systemic reviews and meta-analyses, clinical studies, and case reports. Results: Endothelial dysfunction can be assessed by methods based on reactive hyperemia, such as flow-mediated dilation (FMD) measured by ultrasonography, laser-Doppler flowmetry (LDF), or capillaroscopy. In invasive techniques, intravenous administration of vasodilator substances takes place. Some surveys detected impaired microcirculation in OSA patients compared with healthy individuals. The level of dysfunction depended on the severity of OSA. CPAP treatment significantly improved endothelial function and microvascular blood flow and lowered the inflammatory mediator level. Conclusions: The first-choice treatment—CPAP—reduces the number of apneas and hypopneas during the night, induces the reversal of hypopnea and the chronic inflammatory state, and enhances activation of the sympathetic nervous system. Changes are visible as improved blood flow in both macro- and microcirculation, increased arterial elasticity, and decreased stiffness. Thus, early implementation of adequate treatment could be essential to reduce high cardiovascular risk in patients with OSA.

scholarly journals Disorders of Sleep and Aggression Trait in Women Associated: What Underlies Staying “Woke”?

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Hobgood DK
Keyword(s):  
Nervous System ◽  
Sleep Apnea ◽  
Sympathetic Nervous System ◽  
Dopamine System ◽  
Patient Falls ◽  
Online Test ◽  
Sympathetic Nervous ◽  
Sleep Centers ◽  
The Brain

Narcolepsy is a sleep disorder where the patient falls asleep unwillingly. It is thought to be related to hyper functioning central sleep centers in the brain. Sleep apnea is a disorder of breathing disruption during sleep. Genes of the dopamine system have been implicated with high dopamine: norepinephrine ratio. Since dopamine has also been associated with personality traits, the hypothesis we studied herein was that patients with narcolepsy and sleep apnea would score low in catecholamine settings causing aggression trait. We found that narcolepsy and sleep apnea diagnoses showed significantly lower aggression trait using an online test. The conclusion is that narcolepsy and sleep apnea patients are not aggressive in personality, and since aggressiveness is related to sympathetic nervous system activity, this would be predictable given the role of sympathetic nervous system in wakefulness.

scholarly journals Physical (in)activity-dependent alterations at the rostral ventrolateral medulla: influence on sympathetic nervous system regulation

2010 ◽  
Vol 298 (6) ◽  
pp. R1468-R1474 ◽  
Author(s):  
Patrick J. Mueller
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Organ Systems ◽  
Sympathetic Nervous ◽  
Activity Dependent ◽  
The Brain

A sedentary lifestyle is a major risk factor for cardiovascular disease, and rates of inactivity and cardiovascular disease are highly prevalent in our society. Cardiovascular disease is often associated with overactivity of the sympathetic nervous system, which has both direct and indirect effects on multiple organ systems. Although it has been known for some time that exercise positively affects the brain in terms of memory and cognition, only recently have changes in how the brain regulates the cardiovascular system been examined in terms of physical activity and inactivity. This brief review will discuss the evidence for physical activity-dependent neuroplasticity related to control of sympathetic outflow. It will focus particularly on recent studies from our laboratory and others that have examined changes that occur in the rostral ventrolateral medulla (RVLM), considered one of the primary brain regions involved in the regulation and generation of sympathetic nervous system activity.

scholarly journals Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Costas Tsioufis ◽  
Athanasios Kordalis ◽  
Dimitris Flessas ◽  
Ioannis Anastasopoulos ◽  
Dimitris Tsiachris ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Resistant Hypertension ◽  
Antihypertensive Treatment ◽  
Treatment Options ◽  
Treatment Resistance ◽  
Obstructive Sleep ◽  
Cardiovascular Morbidity And Mortality ◽  
Sympathetic Nervous

Resistant hypertension (RH) is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS) activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

Central sympathetic nervous system reinforcement in obstructive sleep apnoea

2018 ◽  
Vol 39 ◽  
pp. 143-154 ◽  
Author(s):  
Magdalena Wszedybyl-Winklewska ◽  
Jacek Wolf ◽  
Arkadiusz Szarmach ◽  
Pawel J. Winklewski ◽  
Edyta Szurowska ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Obstructive Sleep Apnoea ◽  
Sleep Apnoea ◽  
Obstructive Sleep ◽  
Sympathetic Nervous
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