Up-regulation of bradykinin response in rat and human bladder smooth muscle

Purpose: Responses to bradykinin were investigated in vitro in isolated con trol and hypertrophic smooth muscle strips from rat bladder. Materials and Methods: Bladder hypertrophy was induced by a 10-day period o f partial urinary outflow obstruction. In addition, human bladder strips we re also investigated. Results: Bradykinin (1 nM. to 1 mu M.) caused contractions in all tissues s tudied. In the freshly isolated rat bladder preparations bradykinin induced contractions were similar and of small amplitude in control and hypertroph ic tissues. After a 4-hour equilibratory period contractile responses to br adykinin and the B1 specific bradykinin receptor agonist desArg(9) bradykin in were slightly increased in the controls but there was approximately a 6- fold increase in the hypertrophic muscle strips. After 4 hours of equilibra tion the human bladder strips showed a smaller but still significant increa se in contractile response to bradykinin. Indomethacin, a cyclooxygenase in hibitor, almost abolished the increased response, which suggests that prost anoids are involved in the up-regulated response. The protein synthesis inh ibitor cycloheximide inhibited upregulation by approximately 50% in hypertr ophic and control muscle strips from rat bladder and normal muscle from hum an bladder. Conclusions: These results demonstrate that bradykinin receptor responses a re present in rat and human detrusor muscle and they can be up-regulated in vitro. Experiments on hypertrophic rat bladder revealed that this process is enhanced in hypertrophy.