Effects of doxycycline on voiding behaviour of rats with bladder outlet obstruction

To examine the voiding behaviour changes in rats with bladder outlet obstruction (BOO) while inhibiting matrix metalloproteinase (MMP) activity with doxycycline, as increased MMP activity may be involved in obstruction-induced bladder hypertrophy. Female Sprague-Dawley were divided into eight groups (three rats in each group): normal control (NC) +/- doxycycline, 3 weeks partial BOO (3WPBOO) +/- doxycycline, 6 weeks PBOO +/- doxycycline, and 3 weeks PBOO followed by 3 weeks de-obstruction (3WOD) +/- doxycycline. All rats received the same food and water and were on the same 12 h dark/light cycle housed in metabolic cages. Treatment groups were given doxycycline 15 mg/kg/day subcutaneously twice daily. The voiding variables measured were average voided volume (AV V) and voiding frequency (VF) in 24 h. After completion of the voiding behaviour studies, the rats were killed and their bladders were excised and weighed. The AV Vs were significantly increased (P < 0.05) in all study groups compared with the NC group except for the 3WPBOO-doxycycline and 3WOD-doxycycline groups. The VF was significantly increased (P < 0.05) only in the 3WOD-doxycycline group. The bladder weights were significantly increased after PBOO in all the study groups (P < 0.05), except for the 3WOD group. These data show that MMP inhibition may affect voiding behaviour during the response to BOO or its relief. This is the first clinical demonstration that interfering with a principal target of bladder muscle wall remodelling may have a direct effect on bladder function.