| Summary: | 博士 === 高雄醫學大學 === 醫學研究所 === 99 === A rat model of ovariectomy (Ovx)-induced voiding dysfunction has been established which mimicked the urge incontinence in menopausal women. The present study was designed to investigate the effect of nitric oxide (NO) precursor, L-arginine, on bladder function following Ovx. Twenty-eight female rabbits were separated into seven groups. Groups 1 to 6 underwent Ovx surgery. Among them, groups 1 and 2 received Ovx without treating with L-arginine. Groups 3, 4, 5 and 6 were given high L-arginine diet and were sacrificed 1, 3, 7 and 14 days after Ovx, respectively. Group 7 was served as the control group. The effects of L-arginine on the contractile of bladder tissues were determined in response to various stimulations. In addition, L-arginine effects on the expression of Rho-kinase (ROK), protein kinase C potentiated inhibitor (CPI-17), caldesmon (CaD) and calponin (CaP) were studied by immunoblotting. As a result, long term Ovx significantly increased non-voiding contractions and decreased bladder compliance. Ovx also significantly increased apoptotic cells both in mucosa and in smooth muscle layers and prompted bladder interstitial fibrosis. Additionally, oxidative stress markers, nitrotyrosine and protein carbonylation levels significantly increased in the Ovx group. Therefore, Ovx significantly decreases contractile response to all forms of stimulation. For furture investigation, feeding rabbits L-arginine significantly increases contractile response at 1 day following Ovx but the response decreases to the control level by 14 days. Moreover, Ovx increases the expressions of both isoforms of CaD, CaP and CPI-17, L-arginine treatment induces ROK underexpression while CaP is overexpressed in the early few days of Ovx but returns to the control level at 2 weeks after Ovx. Ovx increased apoptosis, oxidative stress damages in the bladder and induced OAB symptoms. Ovx appreciably reduces bladder contractility, however treatment with L-arginine has potential in the reversal of Ovx-induced bladder dysfunction, decreases in bladder contractile response, especially in the early few days following Ovx.
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