PMID- 33230951 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20210624 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 35 IP - 2 DP - 2021 Feb TI - Intermittent short-duration reoxygenation protects against simulated high altitude-induced pulmonary hypertension in rats. PG - e21212 LID - 10.1096/fj.202000533RR [doi] AB - High-altitude pulmonary hypertension (HAPH) is a severe and progressive disease caused by chronic hypoxia and subsequent pulmonary vascular remodeling. No cure is currently available owing to an incomplete understanding about vascular remodeling. It is believed that hypoxia-induced diseases can be prevented by treating hypoxia. Thus, this study aimed to determine whether daily short-duration reoxygenation at sea level attenuates pulmonary hypertension under high-altitude hypoxia. To this end, a simulated 5000-m hypoxia rat model and hypoxic cultured human pulmonary artery smooth muscle cells were used to evaluate the effect of short-duration reoxygenation. Results show that intermittent, not continuous, short-duration reoxygenation effectively attenuates hypoxia-induced pulmonary hypertension. The mechanisms underlining the protective effects involved that intermittent, short-duration reoxygenation prevented functional and structural remodeling of pulmonary arteries and proliferation, migration, and phenotypic conversion of pulmonary artery smooth muscle cells under hypoxia. The specific genes or potential molecular pathways responsible for mediating the protective effects were also characterised by RNA sequencing. Further, the frequency and the total time of intermittent reoxygenation affected its preventive effect of HAPH, which was likely attributable to augmented oxidative stress. Hence, daily intermittent, not continuous, short-duration reoxygenation partially prevented pulmonary hypertension induced by 5000-m hypoxia in rats. This study is novel in revealing a new potential method in preventing HAPH. It gives insights into the selection and optimisation of oxygen supply schemes in high-altitude areas. CI - (c) 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. FAU - Lyu, Qiang AU - Lyu Q AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. FAU - Bai, Yungang AU - Bai Y AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. FAU - Cheng, Jiuhua AU - Cheng J AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. FAU - Liu, Huan AU - Liu H AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. FAU - Li, Shaohua AU - Li S AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. FAU - Yang, Jing AU - Yang J AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. FAU - Wang, Zhongchao AU - Wang Z AUID- ORCID: 0000-0003-3118-3375 AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. FAU - Ma, Yan AU - Ma Y AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. FAU - Jiang, Min AU - Jiang M AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. FAU - Dong, Dong AU - Dong D AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. FAU - Yan, Yiquan AU - Yan Y AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. FAU - Shi, Qixin AU - Shi Q AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. FAU - Ren, Xinling AU - Ren X AD - Department of Respiratory Diseases, Xi'an, China. FAU - Ma, Jin AU - Ma J AD - Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201123 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - S88TT14065 (Oxygen) SB - IM MH - Altitude Sickness/*complications/therapy MH - Animals MH - Cells, Cultured MH - Humans MH - Hypertension, Pulmonary/etiology/*therapy MH - Male MH - Muscle, Smooth, Vascular/cytology MH - Myocytes, Smooth Muscle/metabolism MH - Oxidative Stress MH - Oxygen/metabolism MH - Oxygen Inhalation Therapy/*methods MH - Rats MH - Rats, Sprague-Dawley MH - Transcriptome OTO - NOTNLM OT - artery remodeling OT - high-altitude pulmonary hypertension OT - human pulmonary artery smooth muscle cells OT - intermittent reoxygenation EDAT- 2020/11/25 06:00 MHDA- 2021/06/25 06:00 CRDT- 2020/11/24 06:11 PHST- 2020/03/06 00:00 [received] PHST- 2020/11/04 00:00 [revised] PHST- 2020/11/09 00:00 [accepted] PHST- 2020/11/25 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2020/11/24 06:11 [entrez] AID - 10.1096/fj.202000533RR [doi] PST - ppublish SO - FASEB J. 2021 Feb;35(2):e21212. doi: 10.1096/fj.202000533RR. Epub 2020 Nov 23.