Alterations in hepatic Na+-K+ transport during endotoxemia in rats.

Abstract

The effects of endotoxemia on overall Na+ and K+ transport in liver cells were studied. Rats were injected with Salmonella enteritidis endotoxin (5 or 10 mg/kg iv), and their blood samples and livers were obtained 4.5 h after injections. The higher, but not the lower, dose of endotoxin induced hypoglycemia and hyperlacticacidemia, which typify the metabolic deteriorations of endotoxic shock. Control (saline-injected) or endotoxemic rat liver slices (0.3 mm thick) were incubated in oxygenated Krebs-Ringer-bicarbonate solution initially at 0.5 degrees C (for 90 min) and then at 37 degrees C (for 60 min) to assess net active Na+ extrusion and K+ reaccumulation. Mean Na+ extrusion and K+ reaccumulation in control rats were 160 and 87 mmol/kg dry wt, respectively. An inhibition of both K+ reaccumulation and Na+ extrusion was seen in liver slices of rats killed 4.5 h after the 10-mg/kg dose of endotoxin. The ATP content of rewarmed (37 degrees C) liver slices of endotoxic (10 mg/kg) rats equaled 80% of the values of corresponding controls. Hepatic membrane permeability to Na+ (PNa+) and K+ (PK+) was calculated using passive cation flux approximations, intracellular [K+] determinations, extracellular [Na+] values, and membrane potential estimations. PNa+ and PK+ values, respectively, were 2.8 and 8.0 X 10(-8) cm X S-1 in control and 4.3 and 7.6 X 10(-8) cm X S-1 in shock rats. These studies indicated a marked inhibition of active Na+-K+ transport and an increased membrane permeability to Na+ with little or no change in permeability to K+ in endotoxic shock rats. Such cation transport derangements in the liver during endotoxic shock could potentially contribute to impairment in hepatic glucose production.