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

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 70; no. 1; pp. 75 - 84
• Main Authors: Revera, Miriam, Salvi, Paolo, Faini, Andrea, Giuliano, Andrea, Gregorini, Francesca, Bilo, Grzegorz, Lombardi, Carolina, Mancia, Giuseppe, Agostoni, Piergiuseppe, Parati, Gianfranco
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.07.2017
• Subjects: 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; Treatment Outcome; Vascular Stiffness - drug effects; Vascular Stiffness - physiology; altitude; altitude sickness; pulse wave analysis; vascular stiffness; pulse wave velocity; hemodynamics; renin–angiotensin system
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.117.09197

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 study22 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 mfrom 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—URLhttps://www.clinicaltrialsregister.eu/. Unique identifier2008-000540-14.