Pinna C, Zanardo R, Cignarella A, Bolego C, Eberini I, Nardi F, Zancan V, Puglisi L
Institute of Pharmacological Sciences, University of Milan, Italy.
Life Sci. 2000;66(7):617-27. doi: 10.1016/s0024-3205(99)00634-7.
Estrogen deficiency is one of the factors involved in the stress incontinence in postmenopausal women, and estrogens have been used clinically in the treatment of urinary disorders during menopause. Sex hormones seem to be also involved in the diabetic changes of urinary bladder and urethra, because ovariectomy causes an increase in the micturition of streptozotocin-diabetic rats. In the present study diabetic and healthy female rats were used to investigate the effect of 17beta-estradiol on mechanical contractions to norepinephrine and to KCI and relaxations to ATP on isolated proximal urethral preparations as well as on contractions to ACh, ATP and KCl on detrusor smooth muscle strips. The data were compared with those obtained in OVX animals, with or without estradiol replacement. The present study showed that ovariectomy decreased the responses to ATP, NE and KCl in urethral preparations, and responses to ATP, ACh and KCl in bladder strips from both healthy and diabetic rats. Diabetes appeared to potentiate the effect of ovariectomy in both tissues. Estrogen replacement was able to recover functional responses in urethras of healthy rats. In diabetic rats, this treatment partially restored ATP-induced responses in both tissues, almost completely restored those to NE in urethra and those to ACh in bladder. This study clearly indicated that abnormalities of urethra and bladder function caused by ovariectomy can be restored by estrogen treatment also in diabetic animals, at least at an early stage of disease.
雌激素缺乏是绝经后女性压力性尿失禁的相关因素之一，雌激素已在临床上用于治疗绝经期间的泌尿系统疾病。性激素似乎也参与膀胱和尿道的糖尿病性改变，因为卵巢切除术会导致链脲佐菌素诱导的糖尿病大鼠排尿增加。在本研究中，使用糖尿病雌性大鼠和健康雌性大鼠来研究17β-雌二醇对离体近端尿道制剂对去甲肾上腺素和氯化钾的机械收缩作用以及对ATP的舒张作用，以及对逼尿肌平滑肌条对乙酰胆碱、ATP和氯化钾的收缩作用的影响。将这些数据与在有或没有雌激素替代的去卵巢动物中获得的数据进行比较。本研究表明，卵巢切除术降低了尿道制剂对ATP、去甲肾上腺素和氯化钾的反应，以及健康和糖尿病大鼠膀胱条对ATP、乙酰胆碱和氯化钾的反应。糖尿病似乎增强了卵巢切除术在两种组织中的作用。雌激素替代能够恢复健康大鼠尿道的功能反应。在糖尿病大鼠中，这种治疗部分恢复了两种组织中ATP诱导的反应，几乎完全恢复了尿道中去甲肾上腺素诱导的反应以及膀胱中乙酰胆碱诱导的反应。这项研究清楚地表明，卵巢切除术引起的尿道和膀胱功能异常在糖尿病动物中也可以通过雌激素治疗得到恢复，至少在疾病的早期阶段是这样。
