Losartan Has No Effect on High Altitude Diuresis or Acute Mountain Sickness in Well-Acclimatizing Individuals.

Delamere, John P., Susie B. Bradwell, Christopher T. Lewis, Alex Clarke, and Arthur R. Bradwell. Losartan has no effect on high altitude diuresis or acute mountain sickness in well-acclimatizing individuals. High Alt Med Biol. 22:96-101, 2021. Introduction: The diuretic response that occurs on ascent to altitude is associated with suppression of aldosterone. We speculated that losartan, an angiotensin II receptor blocker, might further reduce aldosterone activity thereby enhancing the diuresis. Materials and Methods: Twenty subjects (paired for angiotensin converting enzyme genotypes [II:ID:DD] gender and age) were randomized, on a double-blind basis, to either daily losartan, 100 mg, or placebo. During 7 days of motorized ascent from 2,850 to 5,035 m, collections of 24-hour urine output were measured daily with samples taken for sodium (Na+) and potassium (K+) concentrations. In addition, measurements were made of blood gases and aldosterone concentrations. Results: During the main ascent, there were similar progressive increases in 24-hour urine volumes in placebo and losartan groups with no change in Na+ or K+ excretion. There were negative correlations between mean 24-hour urine volumes and PaO2 (r = -0.97, p < 0.03), and the diuretic response and acute mountain sickness scores at 5,053 m (r = -0.51, p < 0.03). There were no significant changes in aldosterone concentrations measured at baseline and at our high point on day 6 within or between the losartan and placebo groups. Conclusion: The high altitude diuretic response was not increased by losartan indicating aldosterone activity was suppressed in individuals on placebo who were acclimatizing well to altitude.

Urinary Alpha-1-Acid Glycoprotein Is a Sensitive Marker of Glomerular Protein Leakage at Altitude.

Talks, Ben J., Susie B. Bradwell, John Delamere, Will Rayner, Alex Clarke, Chris T. Lewis, Owen D. Thomas, and Arthur R. Bradwell. Urinary alpha-1-acid glycoprotein is a sensitive marker of glomerular protein leakage at altitude. High Alt Med Biol. 19:295-298, 2018.-Proteinuria is an established feature of ascent to altitude and may be caused by a loss of negative charges on glomerular capillary walls (GCWs). To test this hypothesis, we measured two similar sized but oppositely charged proteins in urine: negatively charged alpha-1-acid glycoprotein (α1-AGP, 41-43 kDa) and positively charged dimeric lambda free light chains (λ-FLCs, 50 kDa). Twenty-four-hour urinary leakage was compared with albumin, a 66 kDa negatively charged protein. We studied 23 individuals (ages 23-78 years, male = 17) at baseline (140 m) and daily during an expedition to 5035 m. The results showed a significant increase in median urinary leakage of α1-AGP (p < 0.0001; 6.85-fold) and albumin (p = 0.0006; 1.65-fold) with ascent to altitude, but no significant increase in leakage of λ-FLCs (p = 0.39; 1.14-fold). α1-AGP correlated with the daily ascent profile (p = 0.0026) and partial pressure of oxygen (p = 0.01), whereas albumin showed no correlation (p = 0.19). Urinary α1-AGP was a more sensitive marker of altitude proteinuria than urinary albumin and λ-FLCs, and supported the possibility of loss of GCW negative charges at altitude.

Exercise limitation of acetazolamide at altitude (3459 m).

OBJECTIVE: To assess the effect of acetazolamide (Az) on exercise performance during early acclimatization to altitude. METHODS: Az (250 mg twice daily) or placebo was administered for 3 days in a double-blind, randomized manner followed by a rapid ascent to 3459 m in the Italian Alps. Twenty healthy adults (age range, 18-67 years) were tested at 60% of sea-level peak power output for 15 minutes on a bicycle ergometer after 16 to 27 hours of altitude exposure. Exercise performance was measured in relation to peripheral oxygen saturations measured from pulse oximetry (Spo2), Lake Louise acute mountain sickness (AMS) score, and perceived difficulty. RESULTS: At altitude, resting Spo2 was higher in the Az group compared with placebo (P < .001). The highest AMS scores were in 4 of the placebo individuals with the lowest resting Spo2 (P < .05). During the exercise test, Spo2 fell in all but 1 subject (P < .001) and was reduced more in the Az group (P < .01). Four Az and 1 placebo subject were unable to complete the exercise test; 4 of these 5 had the largest fall in Spo2. The perception of exercise difficulty was higher in the Az subjects compared with those taking the placebo (P < .01). There was an age relationship with exercise limitation; 4 of the 9 older than 50 years failed to complete the test whereas only 1 of 11 younger than 50 years failed, and there were no failures in the 6 younger than 30 years (P < .05). CONCLUSIONS: In this study group, and despite higher resting Spo2, Az may have compromised exercise at 3459 m altitude during early acclimatization, particularly in older subjects.