Gap junction expression and the effects of gap junction inhibitors in overactive bladder models: does ovariectomy have a role?

In this study, gap junction expression and the effects of estrogen deficiency and gap junction inhibitors were investigated in overactive bladder models which were created by bladder outlet obstruction.

In our study, we created four groups as control, ovariectomy, bladder outlet obstruction (BOO), and ovariectomy + BOO. We investigated the effects of oxybutynin and 18-alpha glycyrrhetinic acid (18-α-GA) which is a gap junction blocker on isolated detrusor strips. Western blot method was used to measure the level of connexin-43 in detrusor.

Bladder weights were significantly increased in the BOO and ovariectomy + BOO groups (p < 0.05). There was no statistically significant difference in the maximal contraction responses to carbachol between ovariectomy and control groups. In BOO and ovariectomy + BOO groups, contractile responses were significantly prominent with higher doses of carbachol. Oxybutynin-induced relaxant responses of BOO and ovariectomy + BOO groups were significantly higher than control group (p < 0.05). The relaxation effect of 18-a-GA was more effective in the obstruction groups. Among those two groups, the relaxation observed in BOO group was higher than ovariectomy + BOO group in higher doses of 18-a-GA. Connexin-43 expression was increased in BOO group compared with the control group (p = 0.006). Ovariectomy did not change connexin-43 expression alone; however, when combined with BOO, connexin-43 expression decreased significantly (p = 0.023).

Ovariectomy had no effect on the gap junctions in the bladder and bladder overactivity alone. Therefore, obstruction is the main factor that increases the amount of gap junctions, and gap junction blockers are thus more effective in obstruction. However, ovariectomy was shown to decrease the expression of gap junctions and relaxation effect of gap junction blockers, when combined with BOO.