TRANSPLANTATION OF OLFACTORY MUCOSA FOLLOWING SPINAL CORD INJURY IMPROVES VOIDING EFFICIENCY IN RAT

Abstract

INTRODUCTION AND OBJECTIVE: Ischemia followed by reperfusion is an etiology for the progression of bladder dysfunction associated with bladder outlet obstruction and overactive bladder. Cyclic episodes of ischemia-reperfusion lead to both direct ischemic damage and the generation of free radicals including reactive oxygen species (ROS). Hydrogen peroxide (HP) is the one of most important free radical among ROS, nevertheless, its effects on bladder smooth muscle has not been known. Therefore we examined the direct effect of HP on bladder and its mechanism. METHODS: The smooth muscle in the bladder of rats was obtained and strips were prepared. The effects of HP were examined using isometric tension recording. To elucidate the mechanism of contraction by hydrogen peroxide, 10 nM Y-27632 (specific Rho kinase inhibitor) and 10 μM indomethacin (cyclooxygenase inhibitor) were applied. The changes of HP-induced contraction were observed in condition of Ca2+ free physiologic solution and 10 μM vitamin E (an antioxidant) pretreatment. RESULTS: HP at all concentrations (3*10-6 ~ 3*10-2 g%) showed the contractile response in dose dependent manner. When the strips were pretreated with Y-27632 or indomethacin, the contractile responses were significantly inhibited. After pretreatment of 10 μM verapamil or vitamin E, HP induced contraction were decreased significantly. In condition of Ca2+ free physiologic solution, the contractile responses by HP were almost disappeared. CONCLUSIONS: HP has direct contractile responses of the smooth muscle in the bladder, it is thought that that effect is mediated by the activation of cyclooxygenase pathway, Rho kinase pathway and increased sensitivity of calcium ion. Therefore, it is thought that increased ROS including HP may lead to abnormal contraction of bladder smooth muscle in bladder outlet obstruction or overactive bladder.