Arterial hypertension in a murine model of sleep apnea: role of NADPH oxidase 2

J Hypertens. 2014 Feb;32(2):300-5. doi: 10.1097/HJH.0000000000000016.

Abstract

Objectives: To investigate whether NADPH oxidase 2 (NOX2), a major source of reactive oxygen species (ROS), contributes to the emergence of arterial hypertension in a murine model of sleep apnea.

Background: Obstructive sleep apnea (OSA) is a risk factor for arterial hypertension and it is linked to oxidative stress.

Methods: C57BL/6J mice were exposed to chronic intermittent hypoxia (CIH) for 6 weeks (5 days/week, 8 h/day, alternating cycles of hypoxia and normoxia, each lasting 120 s, nadir FiO2: 7%). Blood pressure was monitored by telemetric catheters implanted into the abdominal aorta. Pharmacological inhibition of NOX by apocynin and NOX2-deficient mice were used to assess the role of NOX in CIH-induced arterial hypertension. NOX2 gene expression was measured by real-time PCR in different cardiovascular tissues.

Results: When compared with room air conditions, wild-type mice showed significant blood pressure elevations after exposure to CIH. This response was attenuated after treating animals with apocynin and in NOX2 (=gp91) knockout mice, whereas NOX2 was not upregulated in the heart, aorta, and femoral/carotid arteries of CIH mice.

Conclusion: We suggest that the CIH-induced arterial hypertension is mediated by ROS derived from an activation of NOX2 within cells located outside the cardiovascular system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / pharmacology
  • Animals
  • Blood Pressure / physiology
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Hypertension / enzymology*
  • Hypertension / etiology*
  • Hypertension / physiopathology
  • Male
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NADPH Oxidase 2
  • NADPH Oxidases / antagonists & inhibitors
  • NADPH Oxidases / genetics
  • NADPH Oxidases / physiology*
  • Oxidative Stress
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Risk Factors
  • Sleep Apnea, Obstructive / complications*
  • Sleep Apnea, Obstructive / enzymology*

Substances

  • Acetophenones
  • Enzyme Inhibitors
  • Membrane Glycoproteins
  • RNA, Messenger
  • Reactive Oxygen Species
  • acetovanillone
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • NADPH Oxidases