Control of Oxygen Uptake, Microcirculation and Glucose Release by Circulating Noradrenaline in Perfused Rat Liver

Abstract

The effect of noradrenaline [norepinephrine, NE] on O uptake, on periportal and perivenous O tension at surface acini, on microcirculation and glucose output were studied in isolated rat liver perfused constant flow with Krebs-Henseleit-hydrogen carbonate buffer containing 5 mM glucose and 2 mM lactate. NE at 1 .mu.M concentration caused a decrease in O uptake, while at 0.1 .mu.M it led to an increase. Both high and low doses of NE decreased the tissue surface O tension in periportal and, after a transient rise, in perivenous areas. NE at an overall constant flow caused an increase of portal pressure and an alteration of the intrahepatic distribution of the perfusate: at the surface of the liver and in cross sections infused trypan blue led to only a slightly heterogeneous staining after a low dose of noradrenaline but to a clearly heterogeneous staining after a high dose. Both high and low doses of NE stimulated glucose release. All effects could be inhibited by the .alpha.-blocking agent phentolamine. Control of hepatic O consumption by circulating NE is a complex result of opposing hemodynamic and metabolic components: the microcirculatory changes inhibit O uptake; they dominate after high catecholamine doses. The metabolic effects include a stimulation of O utilization; they prevail at low catecholamine levels. The noradrenergic control of glucose release is also very complex, involving direct, metabolic and indirect, hemodynamic components.