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Conduit artery structure and function in lowlanders and native highlanders : relationships with oxidative stress and role of sympathoexcitation . Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology ( e.g. , chronic mountain sickness ) and methodological issues . We examined vascular function and structure in : ( 1 ) healthy lowlanders during acute hypoxia and prolonged ( ∼2 weeks ) exposure to high altitude , and ( 2 ) high-altitude natives at 5050 m ( highlanders ) . In 12 healthy lowlanders ( aged 32 ± 7 years ) and 12 highlanders ( Sherpa ; 33 ± 14 years ) we assessed brachial endothelium-dependent flow-mediated dilatation ( FMD ) , endothelium-independent dilatation ( via glyceryl trinitrate ; GTN ) , common carotid intima-media thickness ( CIMT ) and diameter ( ultrasound ) , and arterial stiffness via pulse wave velocity ( PWV ; applanation tonometry ) . Cephalic venous biomarkers of free radical-mediated lipid peroxidation ( lipid hydroperoxides , LOOH ) , nitrite ( NO2- ) and lipid soluble antioxidants were also obtained at rest . In lowlanders , measurements were performed at sea level ( 334 m ) and between days 3-4 ( acute high altitude ) and 12-14 ( chronic high altitude ) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level , acute high altitude reduced lowlanders ' FMD ( 7.9 ± 0.4 vs. 6.8 ± 0.4 % ; P = 0.004 ) and GTN-induced dilatation ( 16.6 ± 0.9 vs. 14.5 ± 0.8 % ; P = 0.006 ) , and raised central PWV ( 6.0 ± 0.2 vs. 6.6 ± 0.3 m s ( -1 ) ; P = 0.001 ) . These changes persisted at days 12-14 , and after allometrically scaling FMD to adjust for altered baseline diameter . Compared to lowlanders at sea level and high altitude , highlanders had a lower carotid wall : lumen ratio ( ∼19 % , P ≤ 0.04 ) , attributable to a narrower CIMT and wider lumen . Although both LOOH and NO2- increased with high altitude in lowlanders , only LOOH correlated with the reduction in GTN-induced dilatation evident during acute ( n = 11 , r = -0.53 ) and chronic ( n = 7 , r = -0.69 ; P ≤ 0.01 ) exposure to 5050 m. In a follow-up , placebo-controlled experiment ( n = 11 healthy lowlanders ) conducted in a normobaric hypoxic chamber ( inspired O2 fraction ( F IO 2 ) = 0.11 ; 6 h ) , a sustained reduction in FMD was evident within 1 h of hypoxic exposure when compared to normoxic baseline ( 5.7 ± 1.6 vs. 8.0 ±1.3 % ; P < 0.01 ) ; this decline in FMD was largely reversed following α1-adrenoreceptor blockade . In conclusion , high-altitude exposure in lowlanders caused persistent impairment in vascular function , which was mediated partially via oxidative stress and sympathoexcitation . Although a lifetime of high-altitude exposure neither intensifies nor attenuates the impairments seen with short-term exposure , chronic high-altitude exposure appears to be associated with arterial remodelling .
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Outcome_Physical
carotid wall : lumen
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Participant_Condition
lowlanders and native highlanders :