A low-carbohydrate diet prolongs voiding function and weakens detrusor muscle contraction in rats

Kataoka T1, Hotta Y2, Hamakawa T3, Shibata Y4, Maeda Y2, Ugawa S4, Yasui T3, Kimura K1

Research Type

Basic Science / Translational

Abstract Category

Female Lower Urinary Tract Symptoms (LUTS) / Voiding Dysfunction

Abstract 457
Basic Science: Overactive Bladder and Pain
Scientific Podium Short Oral Session 24
Thursday 30th August 2018
14:15 - 14:22
Hall C
Animal Study Basic Science Underactive Bladder Voiding Dysfunction Pharmacology
1. Department of Clinical Pharmaceutics, Graduate School of Medical Sciences, Nagoya City University, Japan., 2. Department of Hospital Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan., 3. Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City University, Japan., 4. Department of Anatomy and Neuroscience, Graduate School of Medical Sciences, Nagoya City University, Japan.
Presenter
T

Tomoya Kataoka

Links

Abstract

Hypothesis / aims of study
While the number of obese individuals is increasing owing to the Westernization of dietary habits all over the world, many people undertake diet programs. Among the most popular diet programs in recent years, "low-carbohydrate diet (LCD)" is one of the most prevalent. Some people achieved weight loss using this method; however, in a study conducted on more than 40,000 women in Sweden, the group of individuals who were on carbohydrate restricted diets developed an increased risk of experiencing cardiovascular disease and sudden death. These individuals often have such risks and lower urinary tract dysfunction. In this study, we pharmacologically investigated the influence of LCD on lower urinary tract function in rats to try and elucidate the mechanism of development of lower urinary tract disorders.
Study design, materials and methods
We divided 12-week-old female Wistar-ST rats into the control and LCD groups (n = 8 in each group). Rats in the control group were fed a CLEA rodent diet CE-2. On the other hands, rats in the LCD group were raised with a feed in which carbohydrates were replaced with milk casein. Each diet was calculated in similar caloric intake. After 4 weeks, the voiding function 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 by carbachol (10−10 to 10−4 M) and electrical field stimulation (EFS; 1−64 Hz). Moreover, a muscarinic receptor antagonist was used. Real-time PCR was used to examine variations (muscarinic receptors and Rho associated coiled-coil containing protein kinases) in the expression of mRNA in the excised bladder tissue.
Results
The body weight of the rats in the LCD group significantly decreased from one week after LCD administration to 4 weeks. Based on the CMG (80 μL/min) results (Figure A), LCD resulted in a significant prolongation of the voiding interval (LCD group: 1154.5 ± 324.5 sec., control group: 673.5 ± 99.8 sec., Figure B). Intravesical pressure did not differ significantly between the groups (LCD group: 41.6 ± 11.3 cmH2O, control group: 55.0 ± 8.6 cmH2O, Figure C). In contrast, rats on LCD showed a significantly weaker detrusor muscle contractile force in response to carbachol at 10-6 to 10-4-M concentrations (LCD group: 122.8 ± 36.3 N/g, control group: 367.2 ± 158.3 N/g, Figure D). Similarly, rats on LCD showed a weaker contractile force in response to EFS at 2–64 Hz (LCD group: 115.9 ± 9.1 N/g, control group: 357.7 ± 82.6 N/g, Figure E). Adding a muscarinic receptor antagonist did not cause significant differences in the contractile force in response to EFS between the control and LCD groups. The mRNA expression levels of muscarinic receptors (M2 and M3) were significantly lower in the LCD group than in the control group. Rho associated coiled-coil containing protein kinase 2 (ROCK-2) mRNA expression was also significantly lower in the LCD group than in the control group.
Interpretation of results
Our studies showed that LCD could alter the voiding function and detrusor muscle contraction in rats. Interestingly, LCD resulted in the prolongation of the voiding interval. LCD also weakened detrusor muscle contraction in response to carbachol and EFS, though the intravesical pressure as per CMG did not change significantly between the groups. LCD resulted in a decrease in not only M2 and M3 mRNA, but also ROCK-2 mRNA expression. We believe that the down-regulated M2, M3, and ROCK-2 mRNA led to weakened detrusor muscle contraction.
Concluding message
Excessive diet or malnutrition might result in an underactive bladder by decreasing the response of the muscarinic receptors and urinary bladder smooth muscle contractility. Effects of LCD on rats may be induced in a short period of 4 weeks and may be useful as a new under-activity bladder model.
Figure 1
Disclosures
<span class="text-strong">Funding</span> Research grant from the Urakami Foundation for Food and Food Culture Promotion <span class="text-strong">Clinical Trial</span> No <span class="text-strong">Subjects</span> Animal <span class="text-strong">Species</span> Rat <span class="text-strong">Ethics Committee</span> The ethics review board of Nagoya City University