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

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.

• Authors: Richard Schulz, Gulsina Murzabekova, Bakytbek Egemnazarov, Simone Kraut, Hans-Joachim Eisele, Rio Dumitrascu, Jörg Heitmann, Michael Seimetz, Martin Witzenrath, Hossein A Ghofrani, Ralph T Schermuly, Friedrich Grimminger, Werner Seeger, Norbert Weissmann
• Journal: Journal of hypertension (J Hypertens) Vol. 32 Issue 2 Pg. 300-5 (Feb 2014) ISSN: 1473-5598 [Electronic] Netherlands
• PMID: 24270180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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