Abstract：
6-Nitrodopamine (6-ND) is released from human vas deferens and plays a modulatory role in the male ejaculation. Therapeutical use of α1-adrenoceptor antagonists is associated with ejaculatory abnormalities. To evaluate the effect of α1-adrenoceptor antagonists on the contractions induced by 6-ND, dopamine, noradrenaline, and adrenaline in the human epididymal vas deferens (HEVD). HEVD strips were suspended in glass chambers containing heated and oxygenated Krebs-Henseleit\'s solution. Cumulative concentration-response curves to catecholamines (10 nM-300 μM) were constructed in HEVD strips pre-incubated (30 min) with doxazosin (0.1-1 nM), tamsulosin (1-10 nM), prazosin (10-100 nM) and/or silodosin (0.1-10 nM). The effects of these α1-adrenoceptor antagonists were also evaluated in the electric-field stimulation (EFS, 2-32 Hz)-induced contractions. Doxazosin (0.1 nM) caused significant reductions in 6-ND-induced HEVD contractions without affecting the contractions induced by dopamine, noradrenaline, and adrenaline. Similar results were observed with tamsulosin (1 nM) and prazosin (10 nM). At these concentrations, these α1-adrenoceptor antagonists largely reduced the EFS-induced contractions. Silodosin (1 nM) caused concentration-dependent rightward shifts of the concentration-response curves to 6-ND but had no effect on the contractions induced by dopamine and adrenaline. Silodosin (0.1 nM) only inhibited the contractions induced by noradrenaline. Silodosin at 1 nM, but not at 0.1 nM, caused significant reductions in the EFS-induced contractions. The results reinforce the concept that 6-ND plays a major role in the human vas deferens contractility and indicate that the ejaculation disorders caused by doxazosin, tamsulosin, prazosin and silodosin cause in man, may be due to inhibition of the contractions induced by 6-ND rather than by the classical catecholamines dopamine, noradrenaline, and adrenaline.
摘要：
6-硝基多巴胺（6-ND）从人输精管中释放，并在男性射精中起调节作用。α1-肾上腺素受体拮抗剂的治疗用途与射精异常有关。评价α1-肾上腺素受体拮抗剂对6-ND诱导的收缩的影响,多巴胺,去甲肾上腺素,和人附睾输精管（HEVD）中的肾上腺素。将HEVD条悬浮在含有加热和氧化的Krebs-Henseleit溶液的玻璃室中。在与多沙唑嗪（0.1-1nM）预孵育（30分钟）的HEVD条中构建对儿茶酚胺（10nM-300μM）的累积浓度-反应曲线，坦索罗辛(1-10nM),哌唑嗪(10-100nM)和/或西洛多辛(0.1-10nM)。还在电场刺激中评估了这些α1-肾上腺素受体拮抗剂的作用（EFS，2-32Hz）引起的收缩。多沙唑嗪（0.1nM）导致6-ND诱导的HEVD收缩显着减少，而不影响多巴胺诱导的收缩，去甲肾上腺素,和肾上腺素。使用坦索罗辛(1nM)和哌唑嗪(10nM)观察到类似的结果。在这些浓度下，这些α1-肾上腺素受体拮抗剂在很大程度上减少了EFS诱导的收缩.Silodosin（1nM）引起浓度响应曲线对6-ND的浓度依赖性向右移动，但对多巴胺和肾上腺素引起的收缩没有影响。Silodosin（0.1nM）仅抑制去甲肾上腺素诱导的收缩。Silodosin,1nM,但不是0.1nM，导致EFS引起的收缩显着减少。结果强化了6-ND在人类输精管收缩中起主要作用的概念，并表明多沙唑嗪引起的射精障碍，坦索罗辛,哌唑嗪和西洛多辛在人类中引起，可能是由于抑制6-ND而不是经典的儿茶酚胺多巴胺引起的收缩，去甲肾上腺素,和肾上腺素。
