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Up-regulation of bradykinin response in rat and human bladder smooth muscle
R Sjuve1, P J Boels, B Uvelius
1Department of Physiological Sciences, Vascular Biology and Pharmacology Unit, Institute of Child Health, University College, United Kingdom, and Department of Urology, Lund University, Sweden.
Purpose:
Responses to bradykinin were investigated in vitro in isolated control and hypertrophic smooth muscle strips from rat bladder.
Materials And Methods:
Bladder hypertrophy was induced by a 10-day period of partial urinary outflow obstruction. In addition, human bladder strips were also investigated.
Results:
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.
Conclusions:
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.