897 Translocation of nuclear factor-κB and expression of cyclooxygenase-2 is enhanced by ketamine-induced ulcerative cystitis in rat bladder

Abstract

INTRODUCTION AND OBJECTIVES: Hydrogen sulfide (H2S) is a third endogenous gasotransmitter besides NO and CO, and induces smooth muscle relaxation. In this study, we investigated pharmacological profiles of exogenous H2S-induced relaxation of bladder and prostate smooth muscle and expression levels of H2S synthesis enzymes, cystathionine b-synthase (CBS) and 3-mercaptopyruvate sulftransferase (MPST), in these tissues of the rat. METHODS: Bladder dome and trigone (BL-D and BL-T), and ventral and dorsolateral prostate (PR-V and PR-D) were prepared from male Wistar rats (350e400 g). Relaxation effects of NaHS, an H2S donor, were evaluated by organ bath studies on acetylcholine (1x10 5 M)-induced contractions of bladder and on noradrenaline (1x10 5 M)induced ones of prostate. Protein levels of CBS and MPST in each part were also investigated by Western blotting. RESULTS: NaHS dose-dependently elicited relaxation on BL-D and BL-T pre-contracted by acetylcholine and on PR-V and PR-D precontracted by noradrenaline. There were no significant differences in values of EC50 and relaxation rate against the pre-contractions among these tissues. CBS was detected in PR-V and PR-D, and the expression levels in PR-D were higher than those in PR-V. In BL-D and BL-T, CBS was not detected. MPST was detected in all these tissues. Expression levels of MPST in PR-V were the highest and those in prostate were higher than those in bladder. CONCLUSIONS: H2S induces relaxation of bladder and prostate smooth muscle. H2S synthesis enzymes are expressed in both bladder and prostate. These results suggest that H2S could function as an endogenous relaxation factor in both tissues. Endogenous H2S might be a new therapeutic target for lower urinary tract dysfunction such as overactive bladder and benign prostatic hyperplasia. Source of Funding: none