Effect of Suo Quan Wan on the bladder function of aging rats based on the β-adrenoceptor

Abstract

Suo Quan Wan (SQW) has been used to treat lower urinary tract symptoms (LUTS) in elderly patients for hundreds of years in China. β-adrenoceptors (β-ARs), particularly β₃-adrenoceptor (β₃-AR), was reported to be important in the bladder dysfunction of the elderly. The present study was conducted to explore the effect of β-AR, and particularly the β₃-adrenoceptor, in aging rat bladder function in vitro and to test the therapeutic effect of SQW on LUTS in an aging rat model based on the β₃-adrenoceptor. Briefly, the bladder detrusor muscles of young (age, 3 months) and aging (age, 15 months) female rats were separated. A β-AR non-selective agonist, isoprenaline (ISO), subtype β₃-AR agonist (BRL37344A) and β₃-AR antagonist (SR59230A) were used to define the tension change of detrusor muscles between young and aging rats in vitro. For blank controls, 12 young rats were marked, and 48 aging female rats were randomly divided into four groups as follows: Model, SQW high, SQW middle and SQW low. Following oral administration of SQW for 6 weeks in aging rats, urodynamic and bladder detrusor tests were used to evaluate the therapeutic effect of SQW. The expression of β₃-AR mRNA was investigated using reverse transcription-quantitative polymerase chain reaction. Using ISO and BRL37344A in vitro, maximum relaxation (E_max), intrinsic activity (IA), and log (50% effective concentration) (PD₂) were significantly decreased in aging rats compared with that in young rats (P<0.05). Significant changes were also observed in the β₃-AR antagonist experiment, which blocked ISO-induced relaxation, with significant decreases observed in E_max, IA and PD₂, and a significant increase observed in PA₂ for the aging rats compared with the young controls (P<0.05). SQW was demonstrated to enhance bladder control, storage and contraction ability. Furthermore, SQW was able to increase the sensitivity and expression of β₃-AR in an aging rat. In conclusion, the decrease in β₃-AR sensitivity in aging rats and the expression resulted in bladder detrusor dysfunction. In addition, the therapeutic effect of SQW against LUTS relies on the former's effect on the urethral sphincter, bladder detrusor and β₃-AR.

Keywords: Suo Quan Wan; aging rat; bladder detrusor; bladder dysfunction; β-adrenoceptor.

Figure 1.

Effects of SQW on bladder function in aging rats are shown in the bar graphs (A-H), indicating BP, ALPP, EV, MVP, VV, MBC, BC and PVR. Data are expressed as mean ± standard deviation and analyzed by one-way analysis of variance (n=12). *P<0.05, **P<0.01 vs. young controls; ^#P<0.05, ^##P<0.01 vs. model group; ^∆P<0.05, ^∆∆P<0.01 vs. before administration in the same group. SQW, Suo Quan Wan; BP, bladder leak point pressure; ALPP, abdomen leak point pressure; EV, efficiency of voiding; MVP, maximum voiding pressure; VV, voiding volume; MBC, maximum bladder capacity; BC, bladder capacity; PVR, post-void residual.

Figure 2.

Effects of SQW on sphincter in aging rats are shown in the bar graphs (A-C) indicating MUCP, MUP, and FUL. Data are expressed as mean ± standard deviation and analyzed by one-way analysis of variance (n=12). *P<0.05, **P<0.01 vs. young control; ^#P<0.05, ^##P<0.01 vs. model group; ^∆P<0.05, ^∆∆P<0.01 vs. before administration in the same group. SQW, Suo Quan Wan; MUCP, maximum urethral closure pressure; FUL, functional urethral length.

Figure 3.

Effects of SQW on β₃-AR mRNA expressions. Data are expressed as mean ± standard deviation and analyzed by one-way analysis of variance (n=12). **P<0.01 vs. young control; ^#P<0.05 vs. model group. SQW, Suo Quan Wan; AR, adrenoceptor.