Locally released norepinephrine in the oxygen-dependent regulation of vascular tone of human umbilical vein

In a previous study, human umbilical vein preparations constricted at Po-2 values above the physiologic intrauterine Po-2 range and dilated at hypoxia. Denudation of the endothelium reversed the hypoxic vasodilatation only, suggesting the release of a nonendothelial vasoconstrictor. We therefore hypothesized that norepinephrine from adrenergic nerve terminals could be responsible for the observed constricting effects. We measured intracellular membrane potential and isometric tension of human umbilical vein strips with and without functional adrenergic denervation by 6-OH-dopamine during variation of Po-2. With Po-2, increasing from 5 to 104 mm Hg, intact preparations depolarized of from -58.6+/-1.1 mV (SEM) to -53.3+/-1.0 mV (p < 0.001) and isometric tension increased from 0.673+/-0.037 g to 0.825+/-0.044 g (p < 0.02). Intact preparations pretreated with 6-OH-dopamine depolarized from -58.0+/-0.5 mV to -55.8+/-0.6 mV (p < 0.01), and isometric tension increased from 0.598+/-0.040 g to 0.661+/-0.018 g (p < 0.02). At Po-2 values above the physiologic intrauterine umbilical venous Po-2 range, membrane potential and isometric tension were significantly lower in preparations with 6-OH-dopamine pretreatment compared with matched controls (p < 0.05). Denudation of the endothelium reversed the hypoxic hyperpolarization and vasodilatation observed in intact preparations. However, membrane potential and isometric tension were not different between endothelium-denuded preparations with and without 6-OH-dopamine pretreatment. We conclude that locally released norepinephrine contributes to the depolarization and vasoconstriction of the human umbilical vein at hyperoxia but does not antagonize the endothelium-dependent vasodilation at hypoxia.