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Losartan may attenuate altitude-related sleep disturbance
  1. Alexander Clarke1,
  2. C Ladha1,
  3. A Wright2 and
  4. K Pattinson3
  5. Birmingham Medical Research Expeditionary Society
  1. 1 Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK
  2. 2 College of Medical and Dental Sciences, University of Birmingham, Birmingham, Birmingham, UK
  3. 3 Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, Oxfordshire, UK
  1. Correspondence to Dr Alexander Clarke, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, Tyne and Wear NE1 7RU, UK; alexkclarke{at}gmail.com

Abstract

Introduction Sleep disturbance is common at high altitude and likely driven by an exaggerated peripheral chemoreceptor response which leads to apnoeic episodes and arousal. We hypothesised that this heightened response is in part mediated through angiotensin II receptors in the carotid body. To examine this link, we studied the effect of angiotensin II receptor blocker on sleep disturbance.

Methods Twenty participants paired by age, gender and ACE phenotype ascended to the Whymper Hut (5000 m) on Chimborazo in the Ecuadorean Andes as part of a double-blinded randomised placebo-controlled study of physiological mechanisms. Subjects were randomised to either losartan 100 mg daily or placebo. The primary outcome of sleep efficiency was measured using wrist-mounted actigraphs. One pair was excluded from analysis after descending before the end of the study due to acute mountain sickness.

Results There was a significantly different response to altitude between the two groups (F=3.274, p=0.029), as a decline in sleep efficiency in the placebo group (F=10.259, p<0.001) was not replicated in the angiotensin II receptor blocker group (F=0.459, p=0.713).

Conclusion The absence of any significant sleep disturbance in the intervention group suggests that peripheral chemoreceptor hypersensitivity is largely mediated by angiotensin II receptor activation. However, further research is needed to confirm our findings and to study the potential mechanisms of action.

  • sleep
  • periodic breathing
  • losartan
  • angiotensin II receptor
  • altitude
  • actigraphy
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Footnotes

  • Collaborators Birmingham Medical Research Expeditionary Society.

  • Contributors Research conducted on BMRES expedition. Study conception and design: AC, KP. Data collection: AC, AW, CL. Manuscript written by AC and KP.

  • Competing interests KP has acted as a consultant for Nektar Therapeutics. The work for Nektar has no bearing on the contents of this manuscript. KP is named as a co-inventor on a provisional UK patent application titled “Use of cerebral nitric oxide donors in the assessment of the extent of brain dysfunction following injury”.

  • Patient consent for publication Obtained.

  • Ethics approval This physiological mechanisms study was performed according to the Declaration of Helsinki and was approved by Chichester University Research Ethics Committee (protocol no. 1314_42).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

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