Sodium Transport In Epithelial Cells Research Articles

Changes in renal sodium transport during a systemic inflammatory response

Sirs, Watanabe et al. [1] reported on the clinical characteristics of patients with hyponatremia in Kawasaki disease (KD). They noted that hyponatremia was associated with a more severe systemic inflammatory response reflected in prolonged pyrexia and higher C-reactive protein levels. We have recently published the result of a prospective study investigating changes in systemic sodium and chloride transport in meningococcal septicemia. Severe meningococcal septicemia was associated with increased fractional renal sodium excretion [2]. Both meningococcal septicemia and Kawasaki disease are associated with an intensive systemic inflammatory response with high circulating levels of interleukin-1 (IL-1) and tumor necrosis factor (TNF) [3– 6]. The mechanism by which these inflammatory mediators are able to induce hyponatremia has been investigated in both animal studies and in vitro. It involves increased renal sodium loss by a reduction in renal tubular sodium absorption. Inflammatory mediators like IL-1 and TNF have been shown to reduce epithelial sodium transport in epithelial cells by a reduction of the expression and function of the apical epithelial sodium channel (ENaC) and/or the sodium potassium ATPase (Na/K ATPase) at the basolateral membrane [7]. IL-1 was hereby found to induce natriuresis in the rat model [8]. The mechanism was investigated in cultures of inner medullary, cortical collecting duct and proximal tubular renal cells in vitro and it was found to involve a reduction of the Na/K ATPase function. The effect was mediated by prostaglandin E2 and inhibitable by the cyclooxygenase inhibitor indomethacin [9–13]. Another pathway by which IL-1 and TNF are involved in a reduction of renal sodium absorption is by increasing tissue levels of nitric oxide, which is a potent suppressor of the epithelial Na/K ATPase function mediated by the intracellular messenger cGMP and via modification of protein kinase G [14, 15]. Future studies into the etiology of hyponatremia in KD need to investigate the effects of therapies directed at a reduction of effects of IL-1 and TNF and their mediators PGE2 and NO on renal fractional sodium excretion and hyponatremia.

Changes in sodium transport in epithelial cells in a rat ileal-augmented bladder model.

To investigate changes in the morphology and sodium transport ability of intestinal epithelium diverted to the urinary tract, using an in vitro sodium-binding benzofuran isophthalate (SBFI) technique, as the effects of long-term urine exposure on the transport of electrolytes through intestine are incompletely understood. Ileal augmentation cystoplasty was conducted in female Sprague-Dawley rats; at 3 and 12 months after surgery the serum concentration of sodium, chloride and potassium were measured. Sodium transport in the ileal epithelial cells diverted to the urinary tract was evaluated using SBFI, as the value of the 340/380 nm excitation ratio measured with fluorescence spectrophotometry. The villous height and the number of villi per ileal length were obtained from haematoxylin and eosin-stained sections. After 3 months the mean (sd) serum sodium concentrations in normal and augmented rats were 140.4 (2.5) and 140.7 (3.5) mmol/L, respectively; the chloride concentration in normal rats was 97.0 (2.9), and in augmented rats at 3 and 12 months it was 102.4 (2.9) and 99.0 (3.7) mmol/L, respectively. At 3 months, chloride concentrations were significantly higher in augmented than in normal rats (P < 0.05). The mean (sd) 340/380 nm ratio increased by 0.85 (0.09) in the normal ileum, and by 0.73 (0.15) and 0.49 (0.23) in the ileum of augmented rats at 3 and 12 months, respectively; the difference between normal and augmented ileum at 12 months was significant (P < 0.05). At 12 months the villous height in the augmented ileum, at 227.6 (16.0) micro m, was significantly less than in the normal ileum, at 803.4 (66.2) micro m (P < 0.05). However, the number of villi/mm ileum in normal and augmented rats at 12 months was 13.7 (1.5) and 15.0 (0.8), respectively, and not significantly different. Sodium transport decreased significantly after long-term exposure to urine; the improvement in metabolic change was probably attributable to alterations of electrolyte transport and atrophic changes of the villus.

Nitric oxide inhibits transcription of the Na+-K+-ATPase alpha1-subunit gene in an MTAL cell line.

Nitric oxide (NO) has been implicated as an autocrine modulator of active sodium transport. To determine whether tonic exposure to NO influences active sodium transport in epithelial cells, we established transfected medullary thick ascending limb of Henle (MTAL) cell lines that overexpressed NO synthase-2 (NOS2) and analyzed the effects of deficient or continuous NO production [with or without NG-nitro-L-arginine methyl ester (L-NAME) in the culture medium, respectively] on Na+-K+-ATPase function and expression. The NOS2-transfected cells exhibited high-level NOS2 expression and NO generation, which did not affect cell viability or cloning efficiency. NOS2-transfected cells were grown in the presence of vehicle, NG-nitro-D-arginine methyl ester (D-NAME), or L-NAME for 16 h, after which 86Rb+ uptake assays, Northern analysis, or nuclear run-on transcription assays were performed. The NOS2-transfected cells allowed to produce NO continuously (vehicle or D-NAME) exhibited lower rates of ouabain-sensitive 86Rb+ uptake ( approximately 65%), lower levels of Na+-K+-ATPase alpha1-subunit mRNA ( approximately 60%), and reduced rates of de novo Na+-K+-ATPase alpha1-subunit transcription compared with L-NAME-treated cells. These results have uncovered a novel effect of NO to inhibit transcription of the Na+-K+-ATPase alpha1-subunit gene.

Intracellular Redistribution of Sodium and Calcium During Stimulation of Sodium Transport in Epithelial Cells

Intracellular Redistribution of Sodium and Calcium During Stimulation of Sodium Transport in Epithelial Cells