Hypoxic Regulation of Blood Flow in Humans

Abstract

Acute exposure to hypoxia evokes changes in local vasodilator and neural vasoconstrictor factors that significantly influence vascular tone. In humans, the net effect of acute systemic hypoxia is limb vasodilation despite significant reflex increases in muscle sympathetic vasoconstrictor nerve activity and norepinephrine spillover. In this context, some studies in experimental animals and humans have documented that hypoxia can reduce the vasoconstrictor responses to sympathetic nerve stimulation, as well as exogenous α-adrenergic agonist administration (functional sympatholysis). In contrast, other studies have provided evidence that sympathetic vasoconstriction is well preserved during hypoxia. Recently, our laboratory demonstrated that local blockade of α-adrenergic receptors significantly augments the forearm vasodilator response to hypoxia, indicating that sympathetic vasoconstriction persists and can restrain skeletal muscle blood flow under these conditions. Therefore, we revisited this issue and performed a study designed to test the hypothesis that forearm vasoconstrictor responses to local endogenous norepinephrine release are not reduced during systemic hypoxia in humans. To do so, we used selective intra-arterial infusions tyramine to evoke local endogenous norepinephrine release and measured the forearm vasoconstrictor responses during various levels of hypoxia (85, 80, and 75 % O₂ saturation). Our findings demonstrate that forearm post-junctional a-adrenergic vasoconstrictor responsiveness is well preserved during systemic hypoxia in healthy humans. The implications of these findings with respect to arterial blood pressure regulation and functional sympatholysis in skeletal muscle are discussed.