Influence of adjuvant-induced arthritis on the action of extracellular NAD+ on hepatic gluconeogenesis and related parameters

Abstract

The influence of arthritis on some metabolic and hemodynamic effects of extracellular NAD+ was investigated in the perfused liver of Holtzman rats with the additional purpose of comparing the present results with previous results obtained with rats from the Wistar strain. Fasted rats were used and glucose plus pyruvate productions from lactate and the associated oxygen uptake increment were measured as well as the portal perfusion pressure. Livers from arthritic rats presented higher transient increments in perfusion pressure upon NAD+ infusion. The metabolic effects of NAD+ consisted in initial inhibitions of glucose and pyruvate production and oxygen uptake, followed by recovery and stimulation. In the arthritis condition, the inhibitions were more accentuated in relative terms and also more persistent in time, but the subsequent stimulations were smaller or even absent. The inhibitory phase was almost abolished by indomethacin, inhibitor of eicosanoid synthesis, but not by nordihydroguaiaretic acid, an inhibitor of leukotriene synthesis. In comparison with Wistar rats, the response to NAD+ of the liver from Holtzman rats in antegrade perfusion was characterized by a shorter and less intense inhibitory phase and by a more vigorous stimulation. In retrograde perfusion, however, where stimulation was the only effect, there was no difference between both strains. This observation suggests that the more accentuated stimulation in Holtzman rats could be the consequence of a short and less intense inhibitory phase. The stronger and more persistent inhibitions of gluconeogenesis and oxygen uptake as well as the enhanced portal pressure increase in the arthritis condition are consistent with an accentuated capacity of producing eicosanoids by animals under the influence of the disease.