Recently, it has been reported that high salt intake is a risk factor for nocturia[1]. We have reported that a 1 week-long high salt intake in salt sensitive model rats causes urinary storage dysfunction[2]. However, it is not clear what effect high salt intake has on the contractility of the detrusor muscle. In this study, we investigated the effects of high salt intake on the contractile components of the detrusor muscle using salt sensitive model rats.

Six-week-old male Dahl salt-resistant rats (DR rat, n=5) and Dahl salt-sensitive rats (DS rat, n=5) were fed a high salt diet (HS; 8% NaCl) for 1 week. Mean blood pressure was measured at baseline and after 1 week of treatment using a tail-cuff. After the observation period, body weight and bladder weight were measured, and the contractile responses of the detrusor muscle were evaluated by an isometric tension study. In an isometric tension study, contractile responses of the detrusor muscle to high K+ Krebs solution, cumulative administration of carbachol, and electrical field stimulation (EFS) in the absence and presence of inhibitors (suramin; a purinergic receptor inhibitor, atropine; a muscarinic receptor inhibitor and tetrodotoxin; a sodium channel inhibitor) were evaluated. Cholinergic component-related gene expression levels in the bladder were analyzed by real-time PCR.

Mean blood pressure at baseline and 1 week after treatment did not change between the DR+HS and DS+HS groups. The bladder weight to body weight ratio at 1 week after treatment in the DS+HS group was higher than that of the DR+HS group (Fig.1). Contractile responses of the detrusor muscle to the high K+ Krebs solution did not change between the DR+HS group and DS+HS groups. Contractile responses of the detrusor muscle to cumulative carbachol administration in the DS+HS group were increased compared with those in the DR+HS group (Fig.2A). Contractile responses of the detrusor muscle to EFS in the DS+HS group were increased compared with those in the DR+HS group (Fig.2B). From the results of the data analysis under each inhibitor, the purinergic component-induced responses of the detrusor muscle to EFS did not change between the DR+HS and DS+HS groups. On the other hand, muscarinic component-induced responses of the detrusor muscle to EFS in DS+HS group were increased compared with those in DR+HS group (Fig.2C). Cholinergic component-related gene expression levels in the bladder did not changed between the DR+HS and DS+HS groups.

Bladder weight to body weight ratio, contractile responses of the detrusor muscle to cumulative carbachol administration, and EFS and cholinergic component-induced responses of the detrusor muscle were increased in high salt loading salt-sensitive model rats. Increased bladder weight to body weight ratio may suggest that high salt intake causes bladder hypertrophy. Increased contractile responses of the detrusor muscle to cumulative carbachol administration and EFS may suggest that high salt intake enhances signals from the muscarinic receptor. Increased cholinergic component-induced responses  of the detrusor muscle may suggest that high salt intake obstructs bladder extension in urinary storage and decreases bladder capacity.

One week of high salt intake in DS rats caused bladder hypertrophy and increased cholinergic component-induced contractile responses of the detrusor muscle. It is possible that increased detrusor muscle contractile responses by high salt intake lead to urinary storage dysfunction. In the future, clarifying the mechanism of increased cholinergic component-induced responses of the detrusor muscle by high salt intake may lead to an understanding of pathological conditions and the establishment of treatment for urinary storage dysfunction induced by high salt intake.

Matsuo T, Miyata Y, Sakai H. Daily salt intake is an independent risk factor for pollakiuria and nocturia. Int J Urol. 2017; 24: 384-9
Yamamoto S, Hotta Y, Maeda K et al. High salt loading induces urinary storage dysfunction via upregulation of epithelial sodium channel alpha in the bladder epithelium in Dahl salt-sensitive rats. J Pharmacol Sci. 2017; 135: 121-125