Alterations in cutaneous microvascular function at high altitude in lowlanders and highlanders
Authors: Coombs Geoff B , Akins John , Patik Jordan C , Vizcardo‐Galinda Gustavo , Figueroa‐Mujica Joseph , Villafuerte Francisco , Tymko Michael , Ainslie Philip , Brothers Matthew 
Published: June 2021

Microvascular function is impaired in lowlanders at high altitude; however, this impairment was gauged using post‐occlusive reactive hyperemia and the contribution of nitric oxide (NO) to cutaneous vasodilation at high altitude remains unknown. Low molecular O2 at high altitude leads to production of reactive oxygen species (ROS) and reduced NO bioavailability. We therefore tested the hypothesis that vasodilation during a standard local heating protocol, and thus cutaneous microvascular function, is impaired in lowlanders at high altitude by ROS. We further tested whether lifelong residence at high altitude alters microvascular function compared to lowlanders. Four intradermal microdialysis membranes were inserted in the forearms of 11 male lowlanders [age: 30 (8) years; BMI: 24 (2) kg·m−2] at sea level and after two weeks at 4340 m in Cerro de Pasco, Peru. Andean highlanders [n=11; age: 26 (5) years; BMI: 24 (2) kg·m−2] residing permanently in Cerro de Pasco were also tested. The four sites were randomized and pre‐treated with infusions of 1) lactated Ringer's solution (control), 2) 100 μM Apocynin (NADPH oxidase inhibitor), 3) 10 μM Tempol (superoxide scavenger), and 4) 10 μM Allopurinol (xanthine oxidase inhibitor). Skin blood flux was measured continuously at each site via laser‐Doppler flowmetry during the 39°C local heating (NO‐dependent plateau phase), 20 mM L‐NAME (NO synthase inhibitor), and 44°C local heating combined with 28 mM sodium nitroprusside infusion to achieve maximal vasodilation. Data are presented as cutaneous vascular conductance (CVC; flux/mean arterial pressure) as a percentage of maximum.

There was a main group effect (P<0.001) on CVC during 39°C heating with impaired vasodilation in both lowlanders at high altitude and in Andeans [control site: 54 (14) vs. 50 (24)%, respectively] compared to lowlanders at sea level [control site: 73 (19)%]. Similarly, the NO contribution to vasodilation during the 39°C plateau portion (i.e. effect of L‐NAME) was impaired (main group effect P<0.001) in lowlanders after 2 weeks at high altitude compared to sea level [control site: 41 (11) vs 49 (10)%, respectively], and this impairment was more pronounced in Andeans [control site: 32 (21)%]. There was no influence of ROS pathways, assessed via antioxidant infusions, on cutaneous vasodilation throughout the protocol in any group (all main drug effects P>0.05). When values were pooled from both groups and altitudes, local heating plateau CVC (r2=0.18, P=0.02) and the NO contribution to vasodilation (r2=0.13, P=0.04) were both positively correlated with oxygen‐hemoglobin saturation.

These results indicate that high altitude impairs NO‐mediated vasodilation independent of a ROS mechanism but is associated with oxygen‐hemoglobin desaturation. The extent of microvascular impairment is greater in lifelong high altitude residents.

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This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.