Renin-Angiotensin-Aldosterone System Is Not Involved in the Arterial Stiffening Induced by Acute and Prolonged Exposure to High Altitude

Hypertension. 2017 Jul;70(1):75-84. doi: 10.1161/HYPERTENSIONAHA.117.09197. Epub 2017 Jun 5.


This randomized, double-blind, placebo-controlled study was designed to explore the effects of exposure to very high altitude hypoxia on vascular wall properties and to clarify the role of renin-angiotensin-aldosterone system inhibition on these vascular changes. Forty-seven healthy subjects were included in this study: 22 randomized to telmisartan (age, 40.3±10.8 years; 7 women) and 25 to placebo (age, 39.3±9.8 years; 7 women). Tests were performed at sea level, pre- and post-treatment, during acute exposure to 3400 and 5400-m altitude (Mt. Everest Base Camp), and after 2 weeks, at 5400 m. The effects of hypobaric hypoxia on mechanical properties of large arteries were assessed by applanation tonometry, measuring carotid-femoral pulse wave velocity, analyzing arterial pulse waveforms, and evaluating subendocardial oxygen supply/demand index. No differences in hemodynamic changes during acute and prolonged exposure to 5400-m altitude were found between telmisartan and placebo groups. Aortic pulse wave velocity significantly increased with altitude (P<0.001) from 7.41±1.25 m/s at sea level to 7.70±1.13 m/s at 3400 m and to 8.52±1.59 m/s at arrival at 5400 m (P<0.0001), remaining elevated during prolonged exposure to this altitude (8.41±1.12 m/s; P<0.0001). Subendocardial oxygen supply/demand index significantly decreased with acute exposure to 3400 m: from 1.72±0.30 m/s at sea level to 1.41±0.27 m/s at 3400 m (P<0.001), remaining significantly although slightly less reduced after reaching 5400 m (1.52±0.33) and after prolonged exposure to this altitude (1.53±0.25; P<0.001). In conclusion, the acute exposure to hypobaric hypoxia induces aortic stiffening and reduction in subendocardial oxygen supply/demand index. Renin-angiotensin-aldosterone system does not seem to play any significant role in these hemodynamic changes.

Clinical trial registration: URL: Unique identifier: 2008-000540-14.

Keywords: altitude; altitude sickness; hemodynamics; pulse wave analysis; pulse wave velocity; renin–angiotensin system; vascular stiffness.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Altitude Sickness* / complications
  • Altitude Sickness* / metabolism
  • Altitude Sickness* / physiopathology
  • Altitude Sickness* / prevention & control
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / pharmacokinetics
  • Aorta* / drug effects
  • Aorta* / metabolism
  • Aorta* / physiopathology
  • Benzimidazoles* / administration & dosage
  • Benzimidazoles* / pharmacokinetics
  • Benzoates* / administration & dosage
  • Benzoates* / pharmacokinetics
  • Biological Availability
  • Biological Oxygen Demand Analysis / methods
  • Female
  • Hemodynamics / drug effects
  • Hemodynamics / physiology
  • Humans
  • Male
  • Manometry / methods
  • Middle Aged
  • Pulse Wave Analysis / methods
  • Renin-Angiotensin System* / drug effects
  • Renin-Angiotensin System* / physiology
  • Telmisartan
  • Treatment Outcome
  • Vascular Stiffness* / drug effects
  • Vascular Stiffness* / physiology


  • Angiotensin II Type 1 Receptor Blockers
  • Benzimidazoles
  • Benzoates
  • Telmisartan