The reduction of apnea–hypopnea duration ameliorates endothelial dysfunction, vascular inflammation, and systemic hypertension in a rat model of obstructive sleep apnea
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.
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.
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).
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.
KeywordsObstructive sleep apnea Animal model Apnea–hypopnea duration Hypertension
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.
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.
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.
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