UP-REGULATION OF BRADYKININ RESPONSE IN RAT AND HUMAN BLADDER SMOOTH MUSCLE

Abstract

Responses to bradykinin were investigated in vitro in isolated control and hypertrophic smooth muscle strips from rat bladder. Bladder hypertrophy was induced by a 10-day period of partial urinary outflow obstruction. In addition, human bladder strips were also investigated. Bradykinin (1 nM. to 1 microM.) caused contractions in all tissues studied. In the freshly isolated rat bladder preparations bradykinin induced contractions were similar and of small amplitude in control and hypertrophic tissues. After a 4-hour equilibratory period contractile responses to bradykinin and the B1 specific bradykinin receptor agonist desArg9 bradykinin were slightly increased in the controls but there was approximately a 6-fold increase in the hypertrophic muscle strips. After 4 hours of equilibration the human bladder strips showed a smaller but still significant increase in contractile response to bradykinin. Indomethacin, a cyclooxygenase inhibitor, almost abolished the increased response, which suggests that prostanoids are involved in the up-regulated response. The protein synthesis inhibitor cycloheximide inhibited up-regulation by approximately 50% in hypertrophic and control muscle strips from rat bladder and normal muscle from human bladder. These results demonstrate that bradykinin receptor responses are 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.