Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation
Lewis, Nia C. S.
Bailey, Damian M.
duManoir, Gregory R.
Lucas, Samuel J.E.
Cotter, James D.
Young, Ian S.
Burgess, Keith R.
Basnet, Aparna S.
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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 allometricallyscaling 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 (inspiredO2 fraction (FIO2 )=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.
The Journal of Physiology;
Lewis, N., Bailey, D.M., duManoir, G.R., Messinger, L., Lucas, S.J., Cotter, J.D., Donnelly, J., McEneny, J., Young, I.S., Stembridge, M., Burgess, K.R., Basnet, A.S. & Ainslie, P.N. (2014) 'Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation', The Journal of Physiology, 592(5), pp.1009-1024.
This article was published in The Journal of Physiology on 23 January 2014 (online), available free at http://dx.doi.org/10.1113/jphysiol.2013.268615
Cardiff Metropolitan University (Grant ID: Cardiff Metropolian (Internal))
This study was carried out within the framework of the Ev-K2-CNR Project in collaboration with the Nepal Academy of Science and Technology as foreseen by the Memorandum of Understanding between Nepal and Italy, and thanks to contributions from the Italian National Research Council. The authors are grateful to the other members of the UBC International Research Expedition to Mt Everest for invaluable help with logistical planning and implementation of this research study. We are grateful to Professor Daniel Green for useful discussions and feedback on this manuscript.
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