GLOBAL REACH 2018: intra‐arterial vitamin C improves endothelial‐dependent vasodilatory function in humans at high altitude. (30th November 2021)

• Record Type: Journal Article
• Authors: Stone, Rachel M.; Ainslie, Philip N.; Tremblay, Joshua C.; Akins, John D.; MacLeod, David B.; Tymko, Michael M.; DeSouza, Christopher A.; Bain, Anthony R.
• Is Part Of: Journal of physiology. Volume 600:Number 6(2022)
• Page Start: 1373
• Page End: 1383
• Publication Date: 2021-11-30
• Subjects: antioxidants -- ascorbic acid -- high altitude -- vascular function; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP282281
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Abstract: High altitude‐induced hypoxaemia is often associated with peripheral vascular dysfunction. However, the basic mechanism(s) underlying high‐altitude vascular impairments remains unclear. This study tested the hypothesis that oxidative stress contributes to the impairments in endothelial function during early acclimatization to high altitude. Ten young healthy lowlanders were tested at sea level (344 m) and following 4–6 days at high altitude (4300 m). Vascular endothelial function was determined using the isolated perfused forearm technique with forearm blood flow (FBF) measured by strain‐gauge venous occlusion plethysmography. FBF was quantified in response to acetylcholine (ACh), sodium nitroprusside (SNP) and a co‐infusion of ACh with the antioxidant vitamin C (ACh+VitC). The total FBF response to ACh (area under the curve) was ∼30% lower at high altitude than at sea level ( P = 0.048). There was no difference in the response to SNP at high altitude ( P = 0.860). At sea level, the co‐infusion of ACh+VitC had no influence on the FBF dose response ( P = 0.268); however, at high altitude ACh+VitC resulted in an average increase in the FBF dose response by ∼20% ( P = 0.019). At high altitude, the decreased FBF response to ACh, and the increase in FBF in response to ACh+VitC, were associated with the magnitude of arterial hypoxaemia (R 2 = 0.60, P = 0.008 and R 2 = 0.63, P = 0.006, respectively). Collectively, these data support the hypothesis that impairments in vascular endothelial function at high altitude are in part attributable to oxidative stress, a consequence of the magnitude of hypoxaemia. These data extend our basic understanding of vascular (mal)adaptation to high‐altitude sojourns, with important implications for understanding the aetiology of high altitude‐related vascular dysfunction. Key points: Vascular dysfunction has been demonstrated in lowlanders at high altitude (>4000 m). However, the extent of impairment and the delineation of contributing mechanisms have remained unclear. Using the gold‐standard isolated perfused forearm model, we determined the extent of vasodilatory dysfunction and oxidative stress as a contributing mechanism in healthy lowlanders before and 4–6 days after rapid ascent to 4300 m. The total forearm blood flow response to acetylcholine at high altitude was decreased by ∼30%. Co‐infusion of acetylcholine with the antioxidant vitamin C partially restored the total forearm blood flow by ∼20%. The magnitude of forearm blood flow reduction, as well as the impact of oxidative stress, was positively associated with the individual severity of hypoxaemia. These data extend our basic understanding of vascular (mal)adaptation to high‐altitude sojourns, with important implications for understanding the aetiology of high altitude‐related changes in endothelial‐mediated vasodilatory function. Abstract : Abstract figure legend Using the isolated perfused forearm technique, we demonstrate that the forearm blood flow response to acetylcholine is decreased by approximately 30% following 4‐days following rapid ascent to 4, 300 m, compared to sea level responses. There was no difference in the response to sodium nitroprusside, indicating that the impairments are associated with the endothelium, and not the smooth muscle. When acetylcholine was co‐infused with the antioxidant, vitamin C, the forearm blood flow response was partially restored back to sea‐level values, indicating oxidative stress as a contributing mechanism for the endothelial dysfunction. The magnitude of the forearm blood flow impairments at high altitude, as well as the improvements from in‐arterial vitamin C infusion, were positively associated with the individual severity of hypoxemia.