TY - JOUR

T1 - The deleterious effects of acute hypoxia on microvascular and large vessel endothelial function

AU - Jones, Danial

AU - Macdonald, Jamie

AU - Sandoo, Aamer

AU - Oliver, Sam

AU - Rossetti, Gabriella

PY - 2021/8/1

Y1 - 2021/8/1

N2 - Hypoxia is associated with diminished bioavailability of the endothelium-derived vasodilator, nitric oxide (NO). Diminished NO bioavailability can have deleterious effects on endothelial function. The endothelium is a heterogeneous tissue; therefore, a comprehensive assessment of endothelial function is crucial to understand the significance of hypoxia-induced endothelial dysfunction. We hypothesized that acute hypoxia would have a deleterious effect on microvascular and large vessel endothelial function. Twenty-nine healthy adults [24 (SD = 4 ) years of age] completed normoxic and hypoxic [inspired O2 fraction = 0.209] trials in this double-blinded, counterbalanced crossover study. After 30 min, we assessed the laser Doppler imaging-determined perfusion response to iontophoresis of ACh as a measure of endothelium-dependent microvascular function and iontophoresis of sodium nitroprusside as a measure of endothelium-independent microvascular function. After 60 min, we assessed brachial flow-mediated dilatation as a measure of large vessel endothelial function. Thirty minutes of hypoxia reduced endothelium-dependent microvascular function determined by the perfusion response to ACh (median difference (x̃∆) = −109% {interquartile range: 542.7}, P < 0.05), but not endothelium-independent microvascular function determined by the perfusion response to sodium nitroprusside (x̃∆ = 69% {interquartile range: 453.7}, P = 0.6). In addition, 60 min of hypoxia reduced allometrically scaled flow-mediated dilatation compared with normoxia (urn:x-wiley:09580670:media:eph13011:eph13011-math-0001 [95% CI = −1.80, −0.58 (Confidence Intervals)]%, P < 0.001). The decrease in microvascular endothelial function was associated with cardiorespiratory fitness (r = 0.45, P = 0.02). In conclusion, acute exposure to normobaric hypoxia significantly reduced endothelium-dependent vasodilatory capacity in small and large vessels. Collectively, these findings highlight the sensitivity of the microvascular circulation to hypoxic insult, particularly in those with poor cardiorespiratory fitness.

AB - Hypoxia is associated with diminished bioavailability of the endothelium-derived vasodilator, nitric oxide (NO). Diminished NO bioavailability can have deleterious effects on endothelial function. The endothelium is a heterogeneous tissue; therefore, a comprehensive assessment of endothelial function is crucial to understand the significance of hypoxia-induced endothelial dysfunction. We hypothesized that acute hypoxia would have a deleterious effect on microvascular and large vessel endothelial function. Twenty-nine healthy adults [24 (SD = 4 ) years of age] completed normoxic and hypoxic [inspired O2 fraction = 0.209] trials in this double-blinded, counterbalanced crossover study. After 30 min, we assessed the laser Doppler imaging-determined perfusion response to iontophoresis of ACh as a measure of endothelium-dependent microvascular function and iontophoresis of sodium nitroprusside as a measure of endothelium-independent microvascular function. After 60 min, we assessed brachial flow-mediated dilatation as a measure of large vessel endothelial function. Thirty minutes of hypoxia reduced endothelium-dependent microvascular function determined by the perfusion response to ACh (median difference (x̃∆) = −109% {interquartile range: 542.7}, P < 0.05), but not endothelium-independent microvascular function determined by the perfusion response to sodium nitroprusside (x̃∆ = 69% {interquartile range: 453.7}, P = 0.6). In addition, 60 min of hypoxia reduced allometrically scaled flow-mediated dilatation compared with normoxia (urn:x-wiley:09580670:media:eph13011:eph13011-math-0001 [95% CI = −1.80, −0.58 (Confidence Intervals)]%, P < 0.001). The decrease in microvascular endothelial function was associated with cardiorespiratory fitness (r = 0.45, P = 0.02). In conclusion, acute exposure to normobaric hypoxia significantly reduced endothelium-dependent vasodilatory capacity in small and large vessels. Collectively, these findings highlight the sensitivity of the microvascular circulation to hypoxic insult, particularly in those with poor cardiorespiratory fitness.

KW - Cardiorespiratory fitness

KW - endothelium

KW - Iontophoresis

KW - Nitric Oxide

KW - Vasodilation

U2 - 10.1113/EP089393

DO - 10.1113/EP089393

M3 - Article

VL - 106

SP - 1699

EP - 1709

JO - Experimental Physiology

JF - Experimental Physiology

SN - 0958-0670

IS - 8

ER -