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全身应用阿扑吗啡的促勃起作用:脊髓作用位点的存在

Pro-erectile effect of systemic apomorphine: existence of a spinal site of action.

作者信息

Giuliano François, Allard Julien, Rampin Olivier, Droupy Stéphane, Benoit Gérard, Alexandre Laurent, Bernabé Jacques

机构信息

Groupe de Recherche en Urologie, UPRES, Medical University of Paris South, Le Kremlin Bicêtre, France.

出版信息

J Urol. 2002 Jan;167(1):402-6.

PMID:11743364
Abstract

PURPOSE

Apomorphine exerts pro-erectile effects by acting on neurons in the paraventricular nucleus of the hypothalamus. In spinal cord injured rats we assessed whether apomorphine also directly activates the spinal autonomic and somatic neurons controlling penile erection

MATERIALS AND METHODS

Intracavernous and blood pressure was monitored in groups of 10 anesthetized rats to quantify intracavernous pressure increases elicited after intravenous apomorphine. We determined the number and duration of increases, percent of maximum intracavernous pressure/mean diastolic blood pressure using the formula, maximum intracavernous pressure/diastolic blood pressure x 100, area under the intracavernous pressure curve/diastolic blood pressure and sum of the area under the curve/diastolic blood pressure.

RESULTS

Of 2, 10, 50 and 250 microg./kg. intravenous apomorphine 50 microg./kg. induced significant pro-erectile effects and was subsequently used. In spinal cord injured rats 50 microg./kg. intravenous apomorphine significantly increased median maximum intracavernous pressure/diastolic blood pressure x 100 compared with vehicle injection (56 versus 27 seconds, p <0.001), area under the curve/diastolic blood pressure (21 versus 12 seconds, p = 0.07) and the sum of area under the curve/diastolic blood pressure (132 versus 32 seconds, p = 0.01). These pro-erectile effects of apomorphine were prevented by 50 mg./kg. hexamethonium intravenously or bilateral transection of the pelvic nerves. They were not affected by 3 mg./kg. of the peripheral D1/D2 antagonist domperidone intraperitoneally. In spinal cord injured rats subcutaneous pretreatment with 0.2 mg./kg. of the D1 antagonist SCH23390 significantly enhanced apomorphine induced erections, as indicated by an area under the curve/diastolic blood pressure of 23 to 30 seconds (p = 0.003), whereas they were not changed by 25 mg./kg. of the D2 antagonist sulpiride intraperitoneally. Under the same conditions 1 mg./kg. of the central D1/D2 antagonist haloperidol intraperitoneally only reduced the number of responding rats to 5 versus 10 of 10.

CONCLUSIONS

In spinal cord injured rats systemic apomorphine elicits erection by acting at the spinal cord level. This finding suggests that systemic apomorphine elicits penile erections via spinal and supraspinal targets.

摘要

目的

阿扑吗啡通过作用于下丘脑室旁核的神经元发挥促勃起作用。在脊髓损伤大鼠中,我们评估了阿扑吗啡是否也直接激活控制阴茎勃起的脊髓自主神经和躯体神经元。

材料与方法

对10只麻醉大鼠分组监测海绵体内压和血压,以量化静脉注射阿扑吗啡后引起的海绵体内压升高。我们确定了升高的次数和持续时间、使用公式(最大海绵体内压/平均舒张压×100)计算的最大海绵体内压/平均舒张压百分比、海绵体内压曲线下面积/舒张压以及曲线下面积总和/舒张压。

结果

静脉注射2、10、50和250微克/千克阿扑吗啡,50微克/千克可诱导显著的促勃起作用,随后被采用。在脊髓损伤大鼠中,与注射溶媒相比,静脉注射50微克/千克阿扑吗啡显著增加了最大海绵体内压/舒张压×100的中位数(56秒对27秒,p<0.001)、曲线下面积/舒张压(21秒对12秒,p = 0.07)以及曲线下面积总和/舒张压(132秒对32秒,p = 0.01)。阿扑吗啡的这些促勃起作用可被静脉注射50毫克/千克六甲铵或双侧切断盆神经所阻断。它们不受腹腔注射3毫克/千克外周D1/D2拮抗剂多潘立酮的影响。在脊髓损伤大鼠中,皮下预先给予0.2毫克/千克D1拮抗剂SCH23390可显著增强阿扑吗啡诱导的勃起,曲线下面积/舒张压为23至30秒(p = 0.003),而腹腔注射25毫克/千克D2拮抗剂舒必利则无变化。在相同条件下,腹腔注射1毫克/千克中枢D1/D2拮抗剂氟哌啶醇仅使有反应的大鼠数量减少至10只中的5只对10只。

结论

在脊髓损伤大鼠中,全身应用阿扑吗啡通过作用于脊髓水平引发勃起。这一发现表明全身应用阿扑吗啡通过脊髓和脊髓上靶点引发阴茎勃起。

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