Elliott R A, Castleden C M, Miodrag A, Kirwan P
University Department of Medicine for the Elderly, Leicester General Hospital, UK.
Eur J Clin Pharmacol. 1992;43(2):149-55. doi: 10.1007/BF01740662.
We have studied the direct effect of 2 mumol.l-1 diethylstilboestrol on isolated rat and human detrusor muscles. Diethylstilboestrol significantly reduced the amplitude of the contractile response of rat detrusor muscle to stimulation with acetylcholine, carbachol, electrical field stimulation, and 5-hydroxytryptamine. In isolated human bladder it also significantly reduced contractions stimulated with acetylcholine, carbachol, and electrical field stimulation. In depolarized rat detrusor muscle stimulated with different concentrations of calcium ions, the contractile responses were significantly reduced by the addition of diethylstilboestrol. Diethylstilboestrol also significantly reduced the amplitude of contractile response to potassium chloride. The inhibitory action of diethylstilboestrol was enhanced by the reduction of extracellular calcium ions, the maximum contractile response to acetylcholine, carbachol, and electrical field stimulation being reduced by a further 32%, 23%, and 45% respectively. Diethylstilboestrol did not have a significant effect on carbachol-induced contractions in depolarized rat detrusor muscle suspended in a calcium-free environment. Diethylstilboestrol was effective in blocking rat and human detrusor muscle contraction. The likely mechanism is a reduction of the influx of calcium ions into the cell during contraction rather than an effect on intracellular calcium release. These results give support for treating incontinent patients with drugs that block calcium ion uptake, and may suggest a further beneficial effect of oestrogen therapy in postmenopausal women.
我们研究了2μmol·L⁻¹己烯雌酚对离体大鼠和人逼尿肌的直接作用。己烯雌酚显著降低了大鼠逼尿肌对乙酰胆碱、卡巴胆碱、电场刺激和5-羟色胺刺激的收缩反应幅度。在离体人膀胱中，它也显著降低了由乙酰胆碱、卡巴胆碱和电场刺激所诱发的收缩。在用不同浓度钙离子刺激的去极化大鼠逼尿肌中，加入己烯雌酚后收缩反应显著降低。己烯雌酚还显著降低了对氯化钾的收缩反应幅度。细胞外钙离子减少会增强己烯雌酚的抑制作用，对乙酰胆碱、卡巴胆碱和电场刺激的最大收缩反应分别进一步降低32%、23%和45%。在无钙环境中悬浮的去极化大鼠逼尿肌中，己烯雌酚对卡巴胆碱诱发的收缩没有显著影响。己烯雌酚能有效阻断大鼠和人逼尿肌的收缩。可能的机制是在收缩过程中减少钙离子流入细胞，而不是影响细胞内钙释放。这些结果支持使用阻断钙离子摄取的药物治疗尿失禁患者，并可能提示雌激素疗法对绝经后女性有进一步的有益作用。
