High salt loading induces urinary storage dysfunction via upregulation of epithelial sodium channel alpha in the bladder epithelium in Dahl salt-sensitive rats

We aimed to investigate whether high salt intake affects bladder function via epithelial sodium channel (ENaC) by using Dahl salt-resistant (DR) and salt-sensitive (DS) rats. Bladder weight of DR thorn high-salt diet (HS, 8% NaCl) and DS thorn HS groups were significantly higher than those of DR thorn normal-salt diet (NS, 0.3% NaCl) and DS thorn NS groups after one week treatment. We thereafter used only DR thorn HS and DS thorn HS group. Systolic and diastolic blood pressures were significantly higher in DS thorn HS group than in DR thorn HS group after the treatment period. Cystometrogram showed the intercontraction intervals (ICI) were significantly shorter in DS thorn HS group than in DR thorn HS group during infusion of saline. Subsequent infusion of amiloride significantly prolonged ICI in DS thorn HS group, while no intra-group difference in ICI was observed in DR thorn HS group. No intra-or inter-group differences in maximum intravesical pressure were observed. Protein expression levels of ENaCa in the bladder were significantly higher in DS thorn HS group than in DR thorn HS group. ENaCa protein was localized at bladder epithelium in both groups. In conclusion, high salt intake is considered to cause urinary storage dysfunction via upregulation of ENaC in the bladder epithelium with salt-sensitive hypertension, suggesting that ENaC might be a candidate for therapeutic target for urinary storage dysfunction. (c) 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.