Anti-hypotensive treatment and endothelin blockade synergistically antagonize exercise fatigue in rats under simulated high altitude.
Repository Usage Stats
Rapid ascent to high altitude causes illness and fatigue, and there is a demand for effective acute treatments to alleviate such effects. We hypothesized that increased oxygen delivery to the tissue using a combination of a hypertensive agent and an endothelin receptor A antagonist drugs would limit exercise-induced fatigue at simulated high altitude. Our data showed that the combination of 0.1 mg/kg ambrisentan with either 20 mg/kg ephedrine or 10 mg/kg methylphenidate significantly improved exercise duration in rats at simulated altitude of 4,267 m, whereas the individual compounds did not. In normoxic, anesthetized rats, ephedrine alone and in combination with ambrisentan increased heart rate, peripheral blood flow, carotid and pulmonary arterial pressures, breathing rate, and vastus lateralis muscle oxygenation, but under inspired hypoxia, only the combination treatment significantly enhanced muscle oxygenation. Our results suggest that sympathomimetic agents combined with endothelin-A receptor blockers offset altitude-induced fatigue in rats by synergistically increasing the delivery rate of oxygen to hypoxic muscle by concomitantly augmenting perfusion pressure and improving capillary conductance in the skeletal muscle. Our findings might therefore serve as a basis to develop an effective treatment to prevent high-altitude illness and fatigue in humans.
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Therapy, Combination
Endothelin A Receptor Antagonists
Published Version (Please cite this version)10.1371/journal.pone.0099309
Publication InfoRadiloff, Daniel; Zhao, Yulin; Boico, Alina; Blueschke, Gert; Palmer, Gregory; Fontanella, Andrew; ... Schroeder, Thies (2014). Anti-hypotensive treatment and endothelin blockade synergistically antagonize exercise fatigue in rats under simulated high altitude. PLoS One, 9(6). pp. e99309. 10.1371/journal.pone.0099309. Retrieved from https://hdl.handle.net/10161/10340.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
More InfoShow full item record
Gustavo S. Montana Distinguished Professor Emeritus of Radiation Oncology
Mark W. Dewhirst, DVM, PhD is the Gustavo S. Montana Professor of Radiation Oncology and Vice Director for Basic Science in the Duke Cancer Institute. Dr. Dewhirst has research interests in tumor hypoxia, angiogenesis, hyperthermia and drug transport. He has spent 30 years studying causes of tumor hypoxia and the use of hyperthermia to treat cancer. In collaboration with Professor David Needham in the Pratt School of Engineering, he has developed a novel thermally sensitive drug carrying liposom
Associate Professor of Surgery
Our overriding interests are in the fields of tissue engineering, wound healing, biosensors, and long term improvement of medical device implantation. My basic research interests are in the area of physiological mechanisms of optimizing substrate transport to tissue. This broad topic covers studies on a whole animal, whole organ, hemorheological, microvascular, cellular, ultrastructural, and molecular level. The current projects include: 1) control of blood flow and flow distribu
Associate Professor of Medicine
Associate Professor of Radiation Oncology
Greg Palmer obtained his B.S. in Biomedical Engineering from Marquette University in 2000, after which he obtained his Ph.D. in BME from the University of Wisconsin, Madison. He is currently an Associate Professor in the Department of Radiation Oncology, Cancer Biology Division at Duke University Medical Center. His primary research focus has been identifying and exploiting the changes in absorption, scattering, and fluorescence properties of tissue associated with cancer progression and therape
Professor of Medicine
Dr. Piantadosi's laboratory has special expertise in the pathogenic mechanisms of acute organ failure, particularly acute lung injury (ALI), with an emphasis on the molecular regulatory roles of the physiological gases— oxygen, carbon monoxide, and nitric oxide— as they relate to the damage responses to acute inflammation. The basic science focuses on oxidative processes and redox-regulation, especially the molecular mechanisms by which reactive oxygen and nitrogen species trans
Alphabetical list of authors with Scholars@Duke profiles.