The Dahl salt-sensitive rat as a model of nocturnal polyuria

Iwamoto T1, Torimoto K1, Morizawa Y1, Gotoh D1, Hori S1, Miyake M1, Tanaka N1, Fujimoto K1

Research Type

Basic Science / Translational

Abstract Category

Research Methods / Techniques

Abstract 515
Bladder Wall, Microbiome and Nocturia
Scientific Podium Short Oral Session 27
Friday 6th September 2019
10:22 - 10:30
Hall G1
Nocturia Voiding Diary Animal Study
1.Department of Urology, Nara Medical University
Presenter
T

Takashi Iwamoto

Links

Abstract

Hypothesis / aims of study
The causes of nocturia are bladder storage dysfunction, global polyuria, nocturnal polyuria, sleep disorders, or their combinations. Among them, nocturnal polyuria is the main cause of nocturia in approximately 80% of patients. Nocturnal polyuria is associated with hypertension, which is influenced by excessive intake of salt. Clinical studies demonstrated that nocturnal polyuria is associated with high salt intakes and treated by reducing salt intake (1, 2). To our knowledge, only few basic studies have been conducted on nocturia due to nocturnal polyuria maybe because no appropriate animal model of nocturnal polyuria exists. Therefore, we aimed to examine whether salt-sensitive rats fed with a high salt-containing diet would show characteristics of nocturia due to nocturnal polyuria.
Study design, materials and methods
Six-week-old Dahl salt-sensitive rats were divided into three groups (n = 4 each). The rats in group A were fed with a 4%-salt diet; those in group B, with a 2%-salt diet; and those in group C, with a 0.3%-salt diet. The rats were maintained under a 12-hour light/dark cycle (lights turned on automatically at 8:00 a.m.) with free access to water and laboratory food. The rats were put in metabolic cages for 24 hours every week from 0 to 6 weeks since the start of special feeding. We measured the consumption of water, blood pressure, urinary frequency, and voided volume per micturition. We also collected urine and measured the concentration of sodium and catecholamine as markers of sympathetic nerve activity at 0 and 6 weeks.
Results
The mean systolic blood pressure seemed to be higher, though not significantly, in group A than in groups B and C at 5 weeks (175.5 ± 40.6 mmHg vs 135.5 ± 6.2 and 132.0 ± 4.2 mmHg, respectively). The mean water consumption per day was significantly higher in group A than in group C at 5 weeks (53.8 ± 6.7 vs. 33.7 ± 10.4 mL, p < 0.01) and was 42.9 ± 3.2 mL in group B.
[Urinary frequency and volume] The mean urinary frequency (9 times in groups A and B, and 8 times in group C) was not significantly different among the groups at daytime when the rats were generally asleep. The mean sum of urinary volume at daytime was significantly larger in groups A and B than in group C at 5 weeks (10.9 ± 2.3 and 10.2 ± 1.1 mL vs. 6.1 ± 1.7 mL, p < 0.05) (Fig. 1). The mean sum of urinary volume at night, when the rats were generally awake, was significantly larger in groups A and B than in group C at 5 weeks (26.3 ± 4.3 and 20.2 ± 2.3 mL vs. 11.1 ± 5.7 mL, p < 0.05) (Fig. 2). The mean voided volume per micturition was significantly larger in group A than in group C (1.15 ± 0.16 vs. 0.76 ± 0.21 mL, p < 0.05), and was 1.02 ± 0.15 mL in group B.
[Urinary analysis] The sodium secretion amounts were significantly higher in groups A and B than in group C at daytime (91.4 ± 17.1 mg and 68.4 ± 16.6 vs. 19.3 ± 2.5 mg, p < 0.01) and significantly different among groups A, B, and C at night (205.9 ± 30.7 vs. 123.3 ± 10.1 vs. 23.2 ± 5.7 mg, p < 0.001). The secretion amounts of adrenaline, noradrenalin, and dopamine in the daytime were not significantly different among the groups.
Interpretation of results
The Dahl salt-sensitive rats fed with the 2%-salt diet showed no significant hypertension and larger urinary volume than the rats fed with the 0.3%-salt diet (normal diet) at daytime, when the rats were generally sleep. The rats ingested approximately 15% of water consumed 24 hours during the daytime. Approximately 50% of the source of urinary volume at daytime was assumed to be accumulated at night. These characteristics are consistent with those of clinical patients with nocturnal polyuria, in whom hypertension is controlled and water consumption at night is small.
Concluding message
Dahl salt-sensitive rats, which are fed with a 2%-salt diet, are candidates as a model of nocturnal polyuria.
Figure 1
Figure 2
References
  1. Matsuo T, Miyata Y, Sakai H. Daily salt intake is an independent risk factor for pollakiuria and nocturia. Int J Urol 24(5):384-389, 2017
  2. Matsuo T, Miyata Y, Sakai H. Effect of salt intake reduction on nocturia in patients with excessive salt intake. Neurourol Urodyn 38(3):927-933, 2019
Disclosures
<span class="text-strong">Funding</span> TSUMURA & CO. supports this study. <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> Nara Medical University Institutional Animal Care and Use Committee