Alpha-adrenergic receptor blockade by phentolamine increases the efficacy of vasodilators in penile corpus cavernosum.
Alpha-adrenergic receptor blockade by phentolamine increases the efficacy of vasodilators in penile corpus cavernosum.
复制标题
酚妥拉明阻断α-肾上腺素能受体可增加阴茎海绵体血管扩张剂的功效。
DOI：
10.1038/sj.ijir.3900504
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Traish,AM
中科院分区：
文献类型：
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作者：
Kim,NN;Goldstein,I;Moreland,RB;Traish,AM
阴茎小梁平滑肌张力是勃起功能的主要决定因素，受到许多细胞间和细胞内途径的高度调节。介导收缩和松弛的通路之间的相互作用尚未得到详细研究。为此，我们研究了酚妥拉明阻断α肾上腺素受体的功能效应及其与血管扩张剂（西地那非、血管活性肠多肽（VIP）和PGE 1）的相互作用，这些血管扩张剂可提高环核苷酸对阴茎海绵体平滑肌收缩力的作用。在用去氧肾上腺素收缩的海绵体组织条的器官浴制剂中，酚妥拉明显着增强西地那非、VIP和PGE 1诱导的松弛。西地那非、VIP或PGE 1也显着增强酚妥拉明在用去氧肾上腺素收缩的海绵体组织条中诱导的松弛。为了研究主动神经源性输入过程中α肾上腺素能受体阻断和环核苷酸代谢改变的影响，器官浴制剂中的海绵体组织条与非肾上腺素能激动剂内皮素-1收缩，并在不存在或存在酚妥拉明和/或西地那非的情况下进行电场刺激（EFS）。 EFS (5–40 Hz) 通常会引起双相松弛和收缩反应。单独使用酚妥拉明可增强放松并减少或防止 EFS 收缩。西地那非在较低频率（≤ 5 Hz）下增强 EFS 松弛。酚妥拉明和西地那非的组合在所有测试频率下增强了 EFS 诱导的松弛。在 10 nM 酚妥拉明和 30 nM 西地那非存在下，EFS 产生增强的松弛反应，其数量与仅存在 50 nM 西地那非时获得的松弛反应相似。因此，用酚妥拉明阻断α-肾上腺素能受体可增加环核苷酸依赖性血管扩张剂的功效。此外，酚妥拉明可增强放松并减弱收缩，以响应 EFS 期间释放的内源性神经递质。这些发现表明，α-肾上腺素能信号传导的拮抗作用使得其他独立的松弛途径在阴茎小梁平滑肌内占主导地位。
Penile trabecular smooth muscle tone, a major determinant of erectile function, is highly regulated by numerous inter-and intracellular pathways. The interaction between pathways mediating contraction and relaxation has not been studied in detail. To this end, we investigated the functional effects of alpha adrenergic receptor blockade with phentolamine and its interaction with vasodilators (sildenafil, vasoactive intestinal polypeptide (VIP) and PGE 1) that elevate cyclic nucleotides on penile cavernosal smooth muscle contractility. In organ bath preparations of cavernosal tissue strips contracted with phenylephrine, phentolamine significantly enhanced relaxation induced by sildenafil, VIP and PGE 1. Sildenafil, VIP or PGE 1 also significantly enhanced relaxation induced by phentolamine in cavernosal tissue strips contracted with phenylephrine. To study the effects of alpha adrenergic receptor blockade and modification of cyclic nucleotide metabolism during active neurogenic input, cavernosal tissue strips in organ bath preparations were contracted with the non-adrenergic agonist endothelin-1 and subjected to electrical field stimulation (EFS) in the absence or presence of phentolamine and/or sildenafil. EFS (5–40 Hz) typically caused biphasic relaxation and contraction responses. Phentolamine alone enhanced relaxation and reduced or prevented contraction to EFS. Sildenafil enhanced relaxation to EFS at lower frequencies (≤ 5 Hz). The combination of phentolamine and sildenafil enhanced EFS-induced relaxation at all frequencies tested. EFS, in the presence of 10 nM phentolamine and 30 nM sildenafil, produced enhanced relaxation responses which were quantitatively similar to those obtained in the presence of 50 nM sildenafil alone. Thus, blockade of α-adrenergic receptors with phentolamine increases the efficacy of cyclic nucleotide-dependent vasodilators. Furthermore, phentolamine potentiates relaxation and attenuates contraction in response to endogenous neurotransmitters which are released during EFS. These findings suggest that antagonism of α-adrenergic signaling enables other independent relaxatory pathways to predominate within penile trabecular smooth muscle.