We reported, in ICS 2019, that Dahl salt-sensitive rats fed a 2%-salt diet was a candidate model of nocturnal polyuria. Briefly, Dahl salt-sensitive rats fed with a 2%-salt diet do not have severe hypertension, but have a larger urinary volume than rats fed with a 0.3%-salt diet (normal diet) during the daytime, when the rats are generally asleep. The diurnal urine volume is approximately double, or greater, compared with the volume of water ingested over an equal duration. The source of excessive urine volume during the daytime was presumably due to accumulation at night. One of the treatment options for nocturnal polyuria is to promote diuresis during active periods instead of sleep periods. In Japan, edema is often treated with herbal medicines. Choreito is a medicine composed of five crude drugs: chorei, bukuryo, takusha, akyo, and kasseki. In the present study, we aimed to investigate the effects of Choreito on a rat model of nocturnal polyuria (NP).

Six-week-old Dahl salt-sensitive rats were divided into two groups . The rats in group A (n = 6) were fed with a 2%-salt plus 3%-Choreito diet; the rats in group B (n = 4) were fed with a 2%-salt plus 1%-Choreito diet; and the rats in group C (n = 4) were fed with a 2%-salt diet. The rats were maintained under a 12-h light/dark cycle (lights on automatically at 8:00 a.m.) and given free access to water and laboratory food. The rats were placed in metabolic cages for a 24-h period once per week, for 6 weeks consecutively. We measured the consumption of water, urinary frequency, voided volume per micturition, body weight, and blood pressure.

The data at 5 weeks are shown below. The mean systolic blood pressure was significantly lower in group A than in groups B and C (134.1 ± 2.7 vs. 142.8 ± 4.2, and 143.8 ± 3.2 mmHg, respectively; p < 0.01) (Figure 1). The mean water consumption per day was not significantly different among groups A, B, and C. The mean urinary frequency was not significantly different among the groups in the daytime, when the rats were generally asleep (8.8 ± 2.3, 10.5 ± 2.1, and 9.3 ± 1.5 times). The mean total urinary volume in the daytime was not significantly different among the groups (9.2 ± 1.6, 9.3 ± 1.6, and 9.0 ± 1.3 mL; p < 0.05). The mean voided volume per micturition at daytime was not significantly different among the groups (1.08 ± 0.26, 0.89 ± 0.07, and 0.97 ± 0.05 mL). The ratio of urine volume to ingested water during the daytime tended to be smaller in group A than in groups B and C (Figure 2).

The administration of 3% Choreito suppressed the increase in blood pressure due to a 2%-salt diet, suggesting that Choreito suppresses the increase in circulating blood volume due to excessive salt intake. Although the ratio of urine volume to ingested water during the daytime was >2.0 in all rats that were not administered Choreito, the ratio was <2.0 in one-quarter of the rats administered 1% Choreito and in one-half of the rats administered 3% Choreito. According to sample size calculations, the ratios may be significantly smaller in rats administered 3% Choreito if statistical outliers were identified and the number of rats in each group was >10. The mechanism underlying the action of Choreito can be explained based on the diuresis-like effects of chorei, takusha, and bukuryo; the cooling effect of kasseki; and the hemostasis effect of akyo. The diuresis-like effects are thought to be the key component responsible for the efficacy of Choreito in the present study.

Choreito may be effective against NP as it prevents excessive body fluid volume before sleep in Dahl salt-sensitive rats fed with a 2%-salt diet.