6-硝基多巴胺(6-ND)是大鼠离体附睾输精管(RIEVD)中收缩性的内源性调节剂,被认为是发射过程的主要外周介质。使用选择性和非选择性β-肾上腺素能受体拮抗剂与射精失败有关。这里,选择性β1-和β1/β2-肾上腺素能受体拮抗剂对6-ND诱导的RIEVD收缩的影响,多巴胺,去甲肾上腺素,肾上腺素,和电场刺激(EFS)进行了研究。选择性β1-肾上腺素能受体拮抗剂阿替洛尔(0.1和1µM),倍他洛尔(1µM),美托洛尔(1µM)和非选择性β1/β2-肾上腺素能受体拮抗剂普萘洛尔(1和10µM)和吲哚洛尔(10µM)引起浓度-反应曲线向6-ND的显着右移(pA26.41,6.91,6.75,6.47和5.74;对于阿替洛尔,倍他洛尔,美托洛尔,普萘洛尔,和吲哚洛尔),但对多巴胺没有影响,去甲肾上腺素-,和肾上腺素引起的收缩.较高浓度的选择性β1-和β1/β2-肾上腺素能受体拮抗剂的作用(阿替洛尔1µM,倍他洛尔1µM,美托洛尔1µM,普萘洛尔10µM,和吲哚洛尔10µM)也降低了对照EFS诱导的RIEVD收缩,但在从L-NAME治疗的动物获得的RIEVD中没有。选择性β1-肾上腺素受体激动剂RO-363,选择性β2-肾上腺素受体激动剂沙丁胺醇,和选择性β3-肾上腺素受体激动剂米拉贝隆,高达300µM,对RIEVD音调没有影响。结果表明,β1-和β1-/β2-肾上腺素受体拮抗剂在RIEVD中充当6-ND受体拮抗剂,进一步证实了6-ND在RIEVD收缩性中的主要作用。
6-Nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral mediator of the emission process. Use of selective and unselective β-adrenergic receptor antagonists has been associated with ejaculatory failure. Here, the effects of selective β1- and β1/β2-adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline, and electric-field stimulation (EFS) were investigated. The selective β1-adrenergic receptor antagonists atenolol (0.1 and 1 µM), betaxolol (1 µM), and metoprolol (1 µM) and the unselective β1/β2-adrenergic receptor antagonists propranolol (1 and 10 µM) and pindolol (10 µM) caused significant rightward shifts of the concentration-response curve to 6-ND (pA2 6.41, 6.91, 6.75, 6.47, and 5.74; for atenolol, betaxolol, metoprolol, propranolol, and pindolol), but had no effect on dopamine-, noradrenaline-, and adrenaline-induced contractions. The effects of selective β1- and β1/β2-adrenergic receptor antagonists at a higher concentration (atenolol 1 µM, betaxolol 1 µM, metoprolol 1 µM, propranolol 10 µM, and pindolol 10 µM) also reduced the EFS-induced RIEVD contractions in control, but not in RIEVD obtained from L-NAME-treated animals. The selective β1-adrenoceptor agonist RO-363, the selective β2-adrenoceptor agonist salbutamol, and the selective β3-adrenoceptor agonist mirabegron, up to 300 µM, had no effect on the RIEVD tone. The results demonstrate that β1- and β1-/β2-adrenoceptor receptor antagonists act as 6-ND receptor antagonists in RIEVD, further confirming the main role of 6-ND in the RIEVD contractility.