The deleterious effects of acute hypoxia on microvascular and large vessel endothelial function. Issue 8 (5th July 2021)

• Record Type: Journal Article
• Authors: Jones, Danial T.; Macdonald, Jamie H.; Sandoo, Aamer; Oliver, Samuel J.; Rossetti, Gabriella M. K.
• Is Part Of: Experimental physiology. Volume 106:Issue 8(2021)
• Page Start: 1699
• Page End: 1709
• Publication Date: 2021-07-05
• Subjects: cardiorespiratory fitness -- endothelium -- iontophoresis -- nitric oxide -- vasodilatation; Physiology, Experimental -- Periodicals; 571.0724
• DOI: 10.1113/EP089393
• Languages: English
• ISSNs: 0958-0670

Abstract

Abstract : New Findings: What is the central question of this study? The aim was primarily to determine the effect of hypoxia on microvascular function and secondarily whether superior cardiorespiratory fitness is protective against hypoxia‐induced impairment in vascular function. What is the main finding and its importance? Hypoxia reduced endothelium‐dependent but not endothelium‐independent microvascular function. The extent of impairment was twofold higher in the microcirculation compared with the large blood vessels. This study suggests that individuals with superior cardiorespiratory fitness might preserve microvascular function in hypoxia. These findings highlight the sensitivity of the microvascular circulation to hypoxia. Abstract: 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 ( x ¯ Δ = − 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. Abstract :