Acetazolamide (Az) is widely used to prevent and treat the symptoms of acute mountain sickness (AMS) but whether it alters exercise capacity at high altitude is unclear. Az (250 mg twice daily) or placebo were administered to 20 healthy adults (age range, 21-77 years) in a double-blind, randomized manner. Participants ascended over five days to 4559 m, before undertaking an incremental exercise test to exhaustion on a bicycle ergometer, with breath-by-breath gas measurements recorded using a portable gas analysis system. Maximum power output (Pmax) was reduced on Az compared with placebo ( p =0.03), as was maximum O2 uptake (VO2max) (20.7 vs 24.6 mL/kg/min; p =0.06) and maximum expired CO2 (VCO2max) (23.4 vs 29.5 mL/kg/min; p =0.01). Comparing individuals matched for similar characteristics, Az-treated participants had smaller changes than placebo-treated participants in minute ventilation (88 vs 116 L/min: p =0.05), end tidal O2 (6.6 vs 9.3 mm Hg: p =0.009), end-tidal CO2 (−2.3 vs −4.2 mm Hg: p =0.005), VO2max (9.8 vs 13.8 mL/kg/min; p =0.04) and VCO2max (14.7 vs 20.8 mL/kg/min; p =0.009). There was a negative correlation between the mean ages of paired vs placebo-treated individuals and differences in Pmax reductions from base-line to altitude ( r =−0.83: p <0.005) and HRmax at altitude ( r =−0.71; p =0.01). Glomerular filtration rate (measured at sea-level) declined with increasing age ( r =−0.69; p =0.001). Thus, 250mg of Az twice daily reduced exercise performance, particularly in older individuals. The age-related effects of Az may reflect higher tissue concentrations due to reduced drug clearance in older people.

Exposure to high altitude induces hypertension that likely exacerbates arterial hypoxia via pulmonary vasoconstriction and ventilation-perfusion mismatching. Research has shown that inhibition of the renin–angiotensin–aldosterone system (RAAS) via an inhibitor provides an antihypertensive effect at rest during acute exposure to high altitude. Such effects may have benefits for exercise performance given the potential for improved arterial saturation, but has not been studied. PURPOSE: To assess the effects of the RAAS inhibitor losartan on maximal exercise performance at 5000 m. METHODS: Eighteen lowlanders were paired-matched for age, ACE gene status, previous altitude exposure and sex, with each of the pair randomly assigned to a group (men:women: losartan 6:3, placebo 6:3; age 40 ± 18 years; height 175 ± 9 cm; body mass 72.4 ± 12.4 kg; BMI 23.7 ± 2.2 kg/m2). A 100 mg once daily dose of either losartan or placebo (starch) was administered in a double-blind manner for 21 days, which included a slow 8-day ascent to 5000 m (Whymper Hut, Chimborazo, Ecuador). At sea-level and within 48 h of arrival at 5000 m, participants (pairs exercised within ~1 h of each other) completed a graded exercise test (GXT) to exhaustion on a supine cycle ergometer (Alticycle, BMRES). Ventilation (VE) and end-tidal gases were measured breath-by-breath (K4b2, Cosmed), and heart rate (HR, ECG), arterial oxygen saturation (SpO2; pulse oximeter) and beat-to-beat blood pressure (finometer) were measured continuously at rest and during exercise. Data are mean ± SD and group differences at peak power output were analyzed using independent t-tests, with significance set at p<0.05. RESULTS: At 5000 m, resting measures of SpO2 between losartan and placebo groups were not significantly different (79 ± 5 vs. 76 ± 6%, p=0.40). Peak power was similarly reduced relative to sea level (p<0.01) in both groups (down 100 ± 29 vs. 91 ± 28 W, p=0.55), while SaO2 (70 ± 6 vs. 70 ± 5%, p=0.96), VO2peak (31.3 ± 4.6 vs. 34.0 ± 7.2 mL·kg-1·min-1, p=0.35), VE (142 ± 38 vs 146.2 ± 31.2 L·min-1, p=0.81) and HR (146 ± 21 vs 149 ± 24 b·min-1, p=0.78) were similar between groups at peak power, as was the increase in BP from rest to peak power (increased by 31 ± 17 vs. 25 ± 16 mmHg, p=0.71). CONCLUSION: Losartan (100 mg) taken daily for 21 days had no observable effect on exercise performance at 5000 m.

#### Summary points Acute altitude illnesses are potentially serious conditions that can affect otherwise fit individuals who ascend too rapidly to altitude. They include high altitude headache, acute mountain sickness, high altitude cerebral oedema, and high altitude pulmonary oedema. The number of people travelling to altitude for work (soldiers, miners, construction workers, and astronomers) or for recreation (skiing, trekking, mountain biking, and climbing) is rising, and increased media attention towards these activities has also raised the profile of altitude related illness. Typical scenarios in which such illness might occur are a family trek to Everest base camp in Nepal (5360 m), a fund raising climb of Mount Kilimanjaro (5895 m), or a tourist visit to Machu Picchu (2430 m). Awareness of potential altitude related problems is important even for healthcare practitioners working at lower altitude, because patients may ask for advice about the safety of a proposed journey and how to prevent illness at altitude. #### Sources and selection criteria We searched Medline and Google Scholar with no …