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

Abstract

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 alpha-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 (approximately 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 alpha-adrenergic receptor vasoconstrictor responsiveness to endogenous noradrenaline release is not blunted during mild-to-moderate systemic hypoxia in healthy humans.

Figure 1. Forearm vasoconstrictor responses to tyramine during normoxia and mild hypoxia

A, the absolute reductions in forearm blood flow (FBF) and vascular conductance (FVC) to tyramine were slightly greater during mild hypoxia (open bars) compared with normoxia (black bars), most likely due to an elevated baseline level of FBF and FVC. B, however, the percentage reductions in FBF and FVC were similar during both conditions. *P < 0.05vs. normoxia.

Figure 2. Forearm vasoconstrictor responses to tyramine during normoxia and graded hypoxia

A, the absolute reductions in FBF and FVC tended to be greater during graded levels of hypoxia (open bars) compared with normoxia (black bars). B, however, the percentage reductions in FBF and FVC were similar during all conditions. These data indicate that forearm sympathetic neural vasoconstriction is well preserved during systemic hypoxia in humans.