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ROS Signaling in Cardiovascular Dysfunction Associated with Obstructive Sleep Apnea

  • Ganesh K. KumarEmail author
  • Gayatri Raghuraman
  • Nanduri R. Prabhakar
Chapter
  • 716 Downloads
Part of the Respiratory Medicine book series (RM, volume 15)

Abstract

Obstructive sleep apnea (OSA) associated with recurrent apnea is one of the most commonly encountered breathing disorders in adult humans. Patients with OSA are prone to develop hypertension and cardiovascular diseases. Despite its adverse clinical consequences, the mechanism(s) by which recurrent apneas lead to cardiovascular abnormalities is poorly understood. OSA causes periodic decreases in arterial blood O2 or intermittent hypoxia (IH). Available evidence suggests that exposing experimental animals to IH during sleep is sufficient to induce cardiovascular abnormalities similar to those seen in OSA patients. A majority of cross-sectional and prospective studies show that patients with severe OSA exhibit oxidative stress compared to healthy humans. Studies in experimental animals provide evidence for IH-induced ROS generation mediating cardiovascular dysfunction. IH-evoked ROS generation seems to involve activation of NADPH oxidase, inhibition of mitochondrial complex I, and downregulation of antioxidant enzymes. Recent studies have identified hypoxia-inducible factor-1 and 2 as major molecular determinants for sustained oxidative stress elicited by IH. Continuous positive airway pressure treatment, which reduces oxidative stress, appears to be effective in attenuating cardiovascular dysfunction in a subset of OSA patients.

Keywords

Chronic intermittent hypoxia NADPH oxidase Mitochondrial complex I Posttranslational modification S-glutathionylation Hypertension Chemoreflex Baroreflex Sympathetic nerve activity Oxidative stress Prooxidant enzymes Antioxidant enzymes Hypoxia-inducible factor-1 Hypoxia-inducible factor-2 

Abbreviations

AM

Adrenal medulla

CA

Catecholamines

CaMK

Calcium-calmodulin-dependent kinase

ERK

Extracellular signal-regulated kinase

ET-1

Endothelin 1

ETC

Electron transport chain

HIF-1α

Hypoxia-inducible factor-1α

HIF-2α

Hypoxia-inducible factor-2α

HVR

Hypoxic ventilatory response

IH

Intermittent hypoxia

MAP

Mean arterial pressure

MnTMPyP

Manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin

MSNA

Muscle sympathetic nerve activity

Nox

NADPH oxidase

O2·−

Superoxide anion

OSA

Obstructive sleep apnea

PKA

Protein kinase A

PP2A

Protein phosphatase 2A

ROS

Reactive oxygen species

SNA

Sympathetic nerve activity

SOD

Superoxide dismutase

T-BARS

Thiobarbituric acid-reactive substances

TH

Tyrosine hydroxylase

Notes

Acknowledgements

This work is supported by grants from the National Institutes of Health Heart, Lung, and Blood Institute HL-90554, HL-76537, HL-86493, and HL-089616.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ganesh K. Kumar
    • 1
    Email author
  • Gayatri Raghuraman
    • 1
  • Nanduri R. Prabhakar
    • 1
  1. 1.Department of Medicine, The Center for Systems Biology of Oxygen Sensing, Institute for Integrative PhysiologyUniversity of ChicagoChicagoUSA

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