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

Abstract

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 + high-salt diet (HS, 8% NaCl) and DS + HS groups were significantly higher than those of DR + normal-salt diet (NS, 0.3% NaCl) and DS + NS groups after one week treatment. We thereafter used only DR + HS and DS + HS group. Systolic and diastolic blood pressures were significantly higher in DS + HS group than in DR + HS group after the treatment period. Cystometrogram showed the intercontraction intervals (ICI) were significantly shorter in DS + HS group than in DR + HS group during infusion of saline. Subsequent infusion of amiloride significantly prolonged ICI in DS + HS group, while no intra-group difference in ICI was observed in DR + HS group. No intra- or inter-group differences in maximum intravesical pressure were observed. Protein expression levels of ENaCα in the bladder were significantly higher in DS + HS group than in DR + HS group. ENaCα 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.

Effect of salt intake reduction on nocturia in patients with excessive salt intake

“…In short, oxidative stress altered the physiological function of the urothelium and increased bladder sensitivity or sense of urgency in in vivo and in vitro studies, and salt intake was associated with the excessive production of oxidative stress . On the other hand, basic research reported that high salt loading induces urinary storage dysfunction via the upregulation of epithelial sodium channel alpha in the bladder epithelium in Dahl salt‐sensitive rats . Thus, we believe that urgency and urinary incontinence by excessive salt intake are regulated by complex mechanisms.…”

“…29 On the other hand, basic research reported that high salt loading induces urinary storage dysfunction via the upregulation of epithelial sodium channel alpha in the bladder epithelium in Dahl salt-sensitive rats. 30 Thus, we believe that urgency and urinary incontinence by excessive salt intake are regulated by complex mechanisms. There were some limitations in the present study.…”

Effects of High Salt Intake on Detrusor Muscle Contraction in Dahl Salt-Sensitive Rats

“…The relationship between high salt intake and urinary storage symptoms has been evaluated in a few studies. We previously reported that one week of high salt intake in DS rats was associated with upregulated expression of epithelial sodium channel alpha in the bladder epithelium and influenced urinary frequency [12]. Kurokawa et al reported that twelve weeks of high salt intake in DS rats caused urinary storage dysfunction via increased release of ATP and prostaglandin E2 from distended bladder epithelium [13].…”

“…Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats are widely used for basic studies on the relationship between salt intake and disease [14]. We previously reported that one week of high salt intake in DS rats was associated with the upregulation of epithelial sodium channel alpha expression and contributed to urinary frequency [12]. These results suggest that high salt intake in DS rats induces urinary storage symptoms after short-term exposure.…”

“…Moreover, other previous studies reported the relationship between high salt intake and urinary storage symptoms [12,13]. Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats are widely used for basic studies on the relationship between salt intake and disease [14].…”