Failure of systemic hypoxia to blunt α-adrenergic vasoconstriction in the human forearm

Systemic hypoxia in humans evokes forearm vasodilatation despite significant reflex increases in sympathetic vasoconstrictor nerve activity and noradrenaline spillover. We sought to determine whether post-junctional α-adrenergic vasoconstrictor responsiveness to endogenous noradrenaline release is blunted during systemic hypoxia. To do so, we conducted a two-part study in healthy young adults. In protocol 1, we measured forearm blood flow (FBF; venous occlusion plethysmography) and calculated the vascular conductance (FVC) responses to brachial artery infusions of two doses of tyramine (evokes endogenous noradrenaline release) in 10 adults during normoxia and mild systemic hypoxia (85 % O₂ saturation; pulse oximetry of the earlobe). Systemic hypoxia evoked significant forearm vasodilatation as indicated by the increases in FBF and FVC (∼20-23 %; P < 0.05). The low and high doses of tyramine evoked significant reductions in FVC (vasoconstriction) that were similar in magnitude during normoxia (-29 ± 3 and -53 ± 4 %) and mild hypoxia (-35 ± 4 and -58 ± 3 %; P = 0.33). In protocol 2, forearm vasoconstrictor responses to the high dose of tyramine were determined in eight young adults during normoxia and during graded levels of systemic hypoxia (85, 80 and 75 % O₂ saturation). The reductions in FVC were similar during normoxia. (-59 ± 2 %) and the three levels of hypoxia (85 % O₂ saturation, -64 ± 3 %; 80 % O₂ saturation, -62 ± 1 %; 75 % O₂ saturation, -61 ± 3 %; P = 0.37). In both protocols, the tyramine-induced increases in deep venous noradrenaline concentrations were similar during normoxia and all levels of hypoxia. Our results demonstrate that post-junctional α-adrenergic receptor vasoconstrictor responsiveness to endogenous noradrenaline release is not blunted during mild-to-moderate systemic hypoxia in healthy humans.