3.4 No significant change on heart rate (HR) in DSS rats
There was no significant change in HR between each high-salt (8%) group and the sham group. The heart rate was approximately 200 bpm in each group. (Figure 5)
3.5 Water consumption, natriuresis and diuresis
All high-salt (8%) groups exhibited significantly higher water consumption, urination, and urinary sodium excretion compared to the sham low-salt group (P<0.001). (Figure 6-8)
Compared to the vehicle group, all treatment groups showed varying degrees of slight decrease in water consumption, with statistical differences at certain time points (P<0.01, P<0.05). (Figure 6).
The results of the natriuresis study demonstrated that the strongest effect was observed on the first day of treatment, with significant differences compared to the vehicle group (P<0.001, P<0.01, P<0.05). As the treatment duration progressed, the natriuretic effects of all treatment groups gradually diminished. However, on the 28th day of treatment, the LCZ696 group and the middle/high-dose groups of S086 still exhibited significant natriuretic effects (P<0.01, P<0.05). (Figure 7).
Regarding diuresis, significant diuretic effects were observed on the first day of treatment in the LCZ696 group, sacubitril group, and middle/high-dose groups of S086, with statistically significant differences (P<0.001, P<0.01). The EXP3174 group and the low-dose group of S086 showed an increasing trend in diuresis but without statistical significance. Over the course of treatment, the diuretic effects of all treatment groups gradually weakened. However, on the 28th day of treatment, the LCZ696 group and the middle/high-dose groups of S086 still exhibited significant diuretic effects (P<0.05). (Figure 8).