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The reduction of apnea–hypopnea duration ameliorates endothelial dysfunction, vascular inflammation, and systemic hypertension in a rat model of obstructive sleep apnea

  • Hao Wu
  • Qianwen Lv
  • Huina Zhang
  • Yanwen Qin
  • Fang Fang
  • Haili Sun
  • Yongxiang WeiEmail author
Sleep Breathing Physiology and Disorders • Original Article

Abstract

Purpose

We aimed to investigate the effect of obstructive sleep apnea (OSA) and apnea–hypopnea duration on endothelial, ventricular function, blood pressure, and inflammation in a rat model.

Methods

We established a novel rat model of OSA. Wistar rats were randomized to six groups according to 4-week different treatments: (1) OSA (apnea for 60 s in a 90-s window of breathing [60 s/90 s] with anesthesia), (2) OSA 30 s/90 s with anesthesia, (3) partial recovery (60 s/90 s for 2 weeks, followed by 15 s/90 s for 2 weeks with anesthesia), (4) complete recovery (60 s/90 s for 2 weeks with anesthesia, and then normal breathing for 2 weeks), (5) sham (normal breathing in the device with anesthesia), and (6) control group (normal breathing, normal cage, no anesthesia). We recorded blood pressure, endothelial function, left ventricular function, and inflammation at different time points.

Results

Vascular inflammation and endothelial dysfunction occurred in OSA models. More systemic inflammatory and endothelial dysfunction were observed in longer apnea–hypopnea duration group and they were reversed in both partial and complete recovery groups. Left ventricular weight/body weight ratio was significantly higher in the OSA (60s/90s) group than complete recovery, sham, and control groups, which remained unchanged in partial recovery group (p < 0.05).

Conclusions

Longer apnea–hypopnea duration is related to more systemic inflammatory and endothelial dysfunction, and hypertension and cardiac remodeling. These can be reversed after a period of recovery, which indicates that time parameters for assessing OSA, such as apnea–hypopnea duration, should be considered instead of apnea–hypopnea index only.

Keywords

Obstructive sleep apnea Animal model Apnea–hypopnea duration Hypertension 

Notes

Acknowledgements

We thank Dr. Y.Y. Yang and L.Y. Li for technical assistance. Jayant M. Pinto, M.D., from the Section of Otolaryngology-Head and Neck Surgery, in the Department of Surgery, at The University of Chicago, provided useful comments. We thank John E. Sanderson, PhD, from Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, and Ellen Knapp, PhD, from Liwen Bianji, Edanz Group China, for editing the English text of a draft of this manuscript.

Authors’ contributions

WH and WY performed the study design and experiment operation and were major contributors in writing the manuscript. LQ and SH performed the sample preparation and measurement of inflammatory cytokines. ZH performed the isolation of rat thoracic aortas. QY performed the study design and data collection. FF analyzed and interpreted the data. All authors read and approved the final manuscript.

Funding

This study was supported by NSFC (Project 81870335), Beijing Medical Project 2016-4, Beijing Key Laboratory of Upper Airway Dysfunction and Related Cardiovascular Diseases (NO: BZ0377), Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201605) and Beijing Municipal Science & Technology Commission (No. Z141100006014057).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

All procedures were approved by the Animal Care and Use Committee of Capital Medical University (AEEI-2015-107). The investigation conformed to the Guide for the Care and Use of Laboratory Animals published by the U.S. National Institutes of Health (NIH Publication No.85-23, revised 1996).

Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

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ESM 1 (DOCX 25 kb)
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Video 1 (AVI 48425 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Hao Wu
    • 1
  • Qianwen Lv
    • 2
  • Huina Zhang
    • 3
    • 4
  • Yanwen Qin
    • 3
    • 4
  • Fang Fang
    • 3
    • 4
  • Haili Sun
    • 1
  • Yongxiang Wei
    • 1
    Email author
  1. 1.Beijing An Zhen HospitalCapital Medical UniversityBeijingPeople’s Republic of China
  2. 2.Beijing An Zhen Hospital, Capital Medical UniversityBeijing Institute of Heart, Lung and Blood Vessel DiseasesBeijingChina
  3. 3.Beijing An Zhen HospitalCapital Medical UniversityBeijingChina
  4. 4.Key Laboratory of Upper Airway Dysfunction-related Cardiovascular DiseasesBeijing Institute of Heart Lung and Blood Vessel Disease, Sleep CentreBeijingChina

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