Modulation by Oxygen of the Actions of Noradrenaline, Sympathetic Nerve Stimulation and Prostaglandin F2αon Carbohydrate Metabolism and Hemodynamics in Perfused Rat Liver

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Abstract
Rat liver was perfused in situ via the portal vein without recirculation of the perfusate. The perfusion medium contained 5 mM glucose, 2 mM lactate and 0.2 mM pyruvate, and it was equilibrated with different oxygen concentrations so as to vary the rate of oxygen delivery from 4 (normal) to either 12 or 0 .mu.mol .times. min-1 .times. g-1 (U/g). 1) Basal glucose and lactate output were clearly increased when oxygen delivery and therefore uptake were decreased from 4 to 2 and 0 U/g. 2) Noradrenaline caused a marked increase in the output of glucose and lactate and a slight increase in oxygen uptake; it also decreased the rate of flow of the perfusate. Decrease of the oxygen supply did not affect this alteration in the glucose and lactate balance, but it abolished the increase in oxygen uptake and decreased the magnitude of the effect on the perfusion rate. 3) Sympathetic nerve stimulation strongly increased glucose and lactate output and clearly reduced oxygen uptake and perfusate flow. Decreased oxygen delivery caused a decrease in the magnitude of all these changes. 4) Prostaglandin F2.alpha. increased glucose and lactate release and decreased perfusate flow. Decrease of the oxygen supply did not affect the increased glucose and lactate release, but it decreased the magnitude of the effect on the perfusion rate. These results lead to the following major conclusions. Oxygen strongly regulates basal carbohdyrate metabolism, while it does not affect the metabolic actions of noradrenaline and prostglandin F2.alpha.. An adequate oxygen supply is, however, a prerequisite for the hemodynamic actions of noradrenaline and prostaglandin F2.alpha. as well as the matabolic and hemodynamic effects of sympathetic nerve stimulation. These findings are in accordance with the suggestion that in liver the oxygen-dependent synthesis of eicosanoids in non-parenchymal cells is involved in the regulation of hemodynamics by noradrenaline and prostaglandin F2.alpha. and of metabolism and hemodynamics by the sympathetic nerves.