Relationship of Glucose Metabolism to Adrenergic Transmission in Rat Mesenteric Arteries

The vasoconstrictor response of perfused rat mesenteric arteries to stimulation of sympathetic nerve fibers is markedly potentiated by glucose deprivation; this potentiation is abolished or reduced when glucose or other sugars are added. The augmentation of the vasoconstrictor response to nerve stimulation produced by glucose deprivation presumably results from an increased release of the adrenergic transmitter, since (1) the response to injected norepinephrine is much less affected by glucose deprivation and (2) the increase in the vasoconstrictor response to either adrenergic stimulus produced by inhibition of neuronal reuptake by cocaine is unaltered by glucose deprivation. The inhibitory effect of glucose may involve its metabolite(s). Pyruvic and lactic acids inhibit the vasoconstrictor response to nerve stimulation previously augmented by glucose deprivation but do not affect adrenergic transmission in the presence of glucose. Also, the inhibitory effect of glucose on the potentiated response is abolished by the simultaneous infusion of 2-deoxy- D -glucose or iodoacetic acid, inhibitors of glucose metabolism. The inhibitory effect of glucose and its metabolite(s) on adrenergic transmission may also involve changes in the ionic permeability of the nerve terminal. In the absence of glucose, raising the Na + and K + concentrations affects the vasoconstrictor response differently, namely, Na + potentiates and K + attenuates the response. These effects are abolished by addition of glucose. In contrast, the effects of increased concentrations of either Ca 2+ (facilitation) or Mg 2+ (inhibition) on neurotransmission are unaffected by removal or restoration of glucose. We conclude that glucose deprivation does not affect adrenergic transmission by acting directly through Ca 2+ . Rather, glucose deprivation decreases pyruvate and possibly other products of glucose metabolism, and these decreases, in turn, alter the concentrations of Na + and K + within the neuron. These latter changes then enhance the availability of Ca 2+ and, thereby, increase the release of the adrenergic transmitter.