Although the number of obese people are on the rise due to the Westernization of dietary habits worldwide, many people are also known to follow diet plans. Out of all the diet booms in recent years, low-carbohydrate diet (LCD) has been the most prevalent. It has been reported that an excessive diet can cause health damage. Some people succeeded in weight loss by this method, but in a study conducted on more than 40,000 women in Sweden, the group who ingested the carbohydrate restricted diet increased the risk of developing cardiovascular disease and sudden death. These risks and lower urinary tract function are common in many cases. We previously reported that LCD prolonged voiding functions and weakened detrusor muscle contraction in rats. In this study, we investigated the mechanisms of LCD on lower urinary tract function using rats so as to elucidate the developmental mechanism of lower urinary tract disorder.

We divided 12-week-old female Wistar-ST rats into control and LCD groups (n = 14 in each group). After 4 weeks, voiding functions and detrusor muscle contraction were evaluated. Cystometrography (CMG) was performed to assess the voiding interval and intravesical pressure. Detrusor muscle contraction was measured via isometric tension using bladder tissue. Contraction was induced using carbachol and electrical field stimulation (EFS). A muscarinic receptor antagonist was also used. Real-time PCR was performed to examine the variations in mRNA expression in the excised bladder tissue. We investigated Muscarinic receptors (M2 and M3), purinergic receptors (P2X1 and P2X3),  nerve growth factor (NGF), GTP cyclohydrolase 1 (GCH-1), and transient receptor potential cation vanilloid receptor (TRPV-4), epithelial sodium channels (ENaC-α,  ENaC-β and ENaC-γ),  mineralocorticoid receptor (MR), and Rho-associated, coiled-coil containing protein kinases (ROCK-1 and ROCK-2) using specific primers.

The body weight of rats in the LCD group significantly decreased from week 1 after LCD administration to week 4. Based on the CMG (80 μL/min) results (Figure 1A), LCD significantly prolonged the voiding interval (LCD group: 1154.5 ± 324.5 s; control group: 673.5 ± 99.8 s; Figure 1B). However, LCD rats also showed a significantly weaker detrusor muscle contractile force in response to carbachol at 10-6–10-4 M when compared to the control group (LCD group: 122.8 ± 36.3 N/g, control group: 367.2 ± 158.3 N/g, Figure 1C). Similarly, LCD rats showed a weaker contractile force against EFS at 2–64 Hz when compared to the control group (LCD group: 115.9 ± 9.1 N/g, control group: 357.7 ± 82.6 N/g, Figure1 D). Muscarinic (M2 and M3) and purinergic (P2X3) receptor mRNA expression were significantly lower in the LCD group than the control group (Figure 2). Furthermore, NGF, GCH-1, MR and TRPV-4 mRNA levels were significantly lower in the LCD group than the control group. ENaC-α and  ENaC-β mRNA tended to be lower in the LCD group than the control group. ROCK-2 mRNA expression was also significantly lower in the LCD group than the control group.

We showed that LCD could change the voiding function and detrusor muscle contraction in rats. Interestingly, LCD prolonged the voiding interval in this study. LCD also weakened the detrusor muscle contraction via carbachol and EFS, though the intravesicular pressure in CMG did not change significantly between the groups. LCD changes afferent neurons by decreasing the mRNA expression of muscarinic and purinergic receptors. LCD also decreased the expressions of mechanosensor factors (TRPV-4, ENaC-α and  ENaC-β), which were regulated by MR signaling pathway. Furthermore, LCD decreased the nerve growth factors. These changes could influence afferent neuron systems. The LCD also weakened detrusor muscle contraction by decreasing ROCK-2 mRNA expression.

Excessive dieting or malnutrition may cause an underactive bladder by decreasing the response of the muscarinic and purinergic receptors,  mechanosensors and urinary bladder smooth muscles.