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Original Research |

Solnatide demonstrates profound therapeutic activity in a rat model of pulmonary edema induced by acute hypobaric hypoxia and exercise OPEN ACCESS

Qiquan Zhou, MD; Dong Wang, MSc; Yunsheng Liu, PhD; Xiaohong Yang, MSc; Rudolf Lucas, PhD; Bernhard Fischer, PhD
Author and Funding Information

Summary conflict of interest statements

QZ, DW, YL, XY and RL have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

BF is employee of APEPTICO. APEPTICO has a pending patent in this scientific field. BF had no role in the animal experiments, data collection and data analysis.

Department of High altitude geographical and High Altitude Disease, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China; and Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, China

Department of High altitude geographical and High Altitude Disease, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China; and Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, China

Department of High altitude geographical and High Altitude Disease, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China; and Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, China

Department of High altitude geographical and High Altitude Disease, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China; and Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, China

Vascular Biology Center, Division of Pulmonary Medicine, Medical College of Georgia, Augusta University, Georgia, USA

APEPTICO Research and Development, Mariahilferstr 136, Vienna, Austria

Corresponding author information: Bernhard Fischer, APEPTICO Forschung und Entwicklung, Mariahilferstr. 136, 1150 Vienna, Austria.


Copyright 2016, The Authors. All Rights Reserved.


Chest. 2016. doi:10.1016/j.chest.2016.10.030
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Abstract

Background  The synthetic peptide solnatide is a novel pharmacological agent that reduces extravascular lung water, blunts reactive oxygen species production and improves lung function due to its ability to directly activate the epithelial sodium channel ENaC. We aimed to investigate the effect of solnatide in pulmonary edema induced by acute hypobaric hypoxia and exercise in rats, which is considered a model for high altitude pulmonary edema.

Methods  Sprague-Dawley rats were assigned to low altitude control and eight treatment groups. Animals of all groups were subjected to exhaustive exercise in a hypobaric, hypoxic environment simulating an altitude of 4,500 m, followed by simulated ascent to 6,000 m. After 48 h at 6,000 m, rats were given sodium chloride, dexamethasone, aminophylline, MAPK and NLRP3 inhibitor, or one of three different doses of solnatide, once daily for three consecutive days. After three days, arterial blood gas, bronchoalveolar lavage fluid, lung water content, histological and ultra-microstructure analyses were performed. Tight junction protein occludin was assayed by immunohistochemistry.

Results  Rats treated with solnatide had significantly lower BALF protein and LWC than high altitude control rats. Lungs of solnatide-treated rats were intact and showed less hemorrhage and disruption of alveolar-capillary barrier than those of high altitude control animals. Occludin expression was significantly higher in solnatide-treated animals, as compared to high altitude control, dexamethasone- and aminophylline-treated animals.

Conclusions  Solnatide reduced pulmonary edema, increased occludin expression and improved gas-blood barrier function during acute hypobaric hypoxia and exercise in rats. These results provide a rationale for the clinical application of solnatide to patients with pulmonary edema and exposure to high altitude hypoxia environment.


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