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

Abstract

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: https://www.clinicaltrialsregister.eu/ . Unique identifier: 2008-000540-14.