Impaired Na(+)-H+ exchanger activity of hepatocytes in chronic renal failure

Available data indicate that cation transport is impaired in many cells in chronic renal failure (CRF). The information on the activity of the Na(+)-H+ exchanger in CRF is variable, and both increased and reduced activity have been reported. The mechanisms through which CRF may exert an effect on the Na(+)-H+ transport are not known. Data exist indicating that PTH inhibits the Na(+)-H+ exchange in kidney and liver, and this action of hormone is most likely due to its ability to raise cytosolic calcium ([Ca2+]i). Therefore, it is possible that excess PTH in CRF may adversely affect the activity of the Na(+)-H+ antiport. This study examines the activity of Na(+)-H+ antiport, intracellular pH (pHi), and buffering capacity of hepatocytes obtained from rats after 6 wk of CRF, from CRF parathyroidectomized animals, and from CRF rats and normal rats treated with verapamil. The pHi and the buffering capacity of hepatocytes were not different in all groups of animals. The activity of the Na(+)-H+ antiport of hepatocytes from CRF animals was significantly (P < 0.01) lower than in hepatocytes from normal rats, CRF parathyroidectomized rats, CRF rats treated with verapamil, and normal rats treated with verapamil, and the values in the latter four groups of animals were not different. This impaired activity of Na(+)-H+ antiport in CRF was observed in all external concentrations of sodium (25, 50, 75, 100, 125, and 150 mM). Thus, CRF altered the kinetics of the transporter in that its Vmax decreased and its K(m) increased. The data show that: (1) CRF is associated with reduction in the activity of Na(+)-H+ antiport in hepatocytes; (2) this defect is due to the state of secondary hyperparathyroidism of CRF; and (3) excess PTH mediates its effect by elevating [Ca2+]i of hepatocytes because treatment of CRF animals with verapamil, which blocks the PTH-induced rise in [Ca2+]i of these cells, prevented the impairment in the activity of the Na(+)-H+ antiport.