The deleterious effects of acute hypoxia on microvascular and large vessel endothelial functions

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 O-2 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 ((X) over bar Delta) = -109% [interquarti le range: 542.7], P < 0.05), but not endothelium-independent microvascular function determined by the perfusion response to sodium nitroprusside (<(X)over bar>Delta = 69% [interquartile range: 453.7], P = 0.6). In addition, 60 min of hypoxia reduced allometrically scaled flow-mediated dilatation compared with normoxia ((X) over bar Delta = -1.19 [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.

Automated summary

Acute exposure to normobaric hypoxia significantly reduces endothelium-dependent vasodilatory capacity in small and large vessels. The decrease in microvascular endothelial function is associated with cardiorespiratory fitness.