Regulation And Expression By Estrogen Of Nitric Oxide Synthase Activity In The Female Rat Lower Urinary Tract

Objective As the average life-span increase, much more attention had been paid to postmenopausal diseases. The incidence of stress urinary incontinence(SUI) is higher in the old-aged women. It is an important sociological and healthy problem. But the etiology and pathophysiology of SUI is still uncertain. Since the incidence of SUI increase after menopause, it is reasonable to believe that estrogen deficiency might be, at least in part, responsible for this disorder. However, to date research on the success of estrogen replacement therapy has been laden with controversy. Some studies show that estrogen replacement therapy for treating postmenopausal stress urinary incontinence is worse than placebo[1]. Recent reports have shown as a non-adrenergic and non-cholinergic (NANC) neuro-transmitter, NO led to urethra smooth muscle relaxation. NO maybe the possible reason for the occurrence of stress urinary incontinence. The model was established for measuring the level of estrogen and nitric oxide in peripheral blood, the changes of smooth muscle and connective tissue in bladder and NO and NOS activity in Isolated urethra and bladder. These results explain the function of the lower urinary tract, histological changes, the relationship among estrogen, NO and SUI after given different doses of estrogen.Method: 50 Sprague-Dawley female rats weighing (200±25)g were bilaterally ovariectomized. Two weeks later 34 rats model were chosen and divided into 4 groups by chance. The control rats received no further treatment except injecting normal sodium, and others were given an intramuscular injection of 0.5mg/kg,1mg/kg or 1.5mg/kg diethylstilbestrol for two weeks. After scarification, the level of estradiol and NO in peripheralblood, smooth muscle/connective tissue of bladder were be detected. Isolated urethra and bladder were cut to determine the level of NO and NOS activity.Result:1 The level of estradiol in vivo was increased after replacement therapy. There were a significant difference in control and experimental groups, but no difference between every experimental groups.2 The content of NO in peripheral blood is higher than the control group, the relationship between estradiol and NO is direct.3 In ovariectomy plus estrogen replacement groups, smooth muscle was thicker, muscle cell was more hypertrophy and compacter and submucous layer was thinner. Histological studies showed a higher smooth muscle to connective tissue ratio than in the control group. Furthermore, we found a negative correlation of estradiol in vivo with the smooth muscle to connective tissue ratio.4 nNOS in the rat lower urinary tract was expressed mainly in the epithelium, smooth muscle and striated muscle which is dark brown stain in cytoplasm. Compared with nNOS in bladder, the expression of nNOS in urethra was higher. The level of NO and nNOS in urethra was significantly decrease in the estrogen groups.5 When the data were compared for samples, we detected a negative correlation of estradiol in vivo with NO and nNOS in the lower urinary tract which to show a positive correlation.Conclusion: A bilaterally ovariectomized rat was considered a more credible model. NO which was not play a role in the target organ by blood circulation was released only through partial tissues in physiological conditions, so NO in peripheral blood is not be the reason for SUI. Estrogen replacement which is changed in urethra function and architectonic is beneficial for treating postmenopausal SUI. Maybe the mechanism is estrogen treatment can decrease NO mediated and neurogenic urethral relaxation through NO/cGMP system.