Cellek S
The Wolfson Institute for Biomedical Research, University College London, London, UK.
Drugs Today (Barc). 2000 Feb-Mar;36(2-3):135-46. doi: 10.1358/dot.2000.36.2-3.568787.
Penile erection is regulated by two opposing systems: noradrenergic (anti-erectile) and nitrergic (pro-erectile) neurotransmission. Noradrenaline released from sympathetic nerves causes contraction of the blood vessels and smooth muscle of the penile corpus cavernosum, thus leading to detumescence of the penis. Nitric oxide (NO) released from nitrergic nerves causes relaxation of the smooth muscle of the corpus cavernosum, thus allowing engorgement of blood into the cavernous space and leading to erection. Nitrergic neurotransmission is known to modulate noradrenergic responses. We have recently shown that the degree of this modulation varies among species. In the human corpus cavernosum, noradrenergic responses are under nitrergic control, such that even pharmacological concentrations of noradrenaline fail to show an effect when nitrergic neurotransmission is operating. This situation is similar in the monkey and rabbit, where nitrergic neurotransmission does not merely modulate but actually controls the sympathetic responses; however it differs in the rat, mouse and dog where the sympathetic system is predominant. Our recent work has demonstrated that the interaction between the two systems occurs in the smooth muscle, suggesting a physiological antagonism. Our observations suggest that the key element in this interaction is intracellular calcium in the smooth muscle. The nitrergic pathway causes a decrease in intracellular calcium concentrations thus leading to relaxation of the smooth muscle. Noradrenergic stimulation, in contrast, elicits an increase in the intracellular calcium concentrations thus leading to a contraction. The neuronal pathway which controls the concentrations of intracellular calcium in the smooth muscle determines the dominance of that pathway over the other. Nitrergic dominance over noradrenergic system in the human corpus cavernosum also suggests a key role for this interaction in the pathophysiology of erectile dysfunction. Indeed, a nitrergic-noradrenergic imbalance in favor of the noradrenergic system has been implicated in penile tissues from patients with erectile dysfunction. However, the mechanism of this imbalance is not fully understood. In addition, since the present study has demonstrated that phosphodiesterase type V inhibitors can enhance and prolong the nitrergic control of noradrenergic responses, such compounds may have therapeutic potential in impotence, where defective nitrergic transmission is accompanied by increased noradrenergic activity.
去甲肾上腺素能（抗勃起）和一氧化氮能（促勃起）神经传递。交感神经释放的去甲肾上腺素会导致阴茎海绵体的血管和平滑肌收缩，从而导致阴茎疲软。一氧化氮能神经释放的一氧化氮（NO）会使海绵体平滑肌松弛，从而使血液充盈到海绵体间隙并导致勃起。已知一氧化氮能神经传递会调节去甲肾上腺素能反应。我们最近发现，这种调节的程度在不同物种之间有所不同。在人类海绵体中，去甲肾上腺素能反应受一氧化氮能控制，以至于当一氧化氮能神经传递起作用时，即使是药理浓度的去甲肾上腺素也无法显示出效果。猴子和兔子的情况类似，在那里一氧化氮能神经传递不仅调节而且实际上控制交感反应；然而，在大鼠、小鼠和狗中情况有所不同，在这些动物中交感神经系统占主导地位。我们最近的研究表明，这两种系统之间的相互作用发生在平滑肌中，表明存在生理拮抗作用。我们的观察结果表明，这种相互作用的关键因素是平滑肌中的细胞内钙。一氧化氮能途径会导致细胞内钙浓度降低，从而导致平滑肌松弛。相比之下，去甲肾上腺素能刺激会引起细胞内钙浓度升高，从而导致收缩。控制平滑肌细胞内钙浓度的神经途径决定了该途径相对于另一种途径的优势。人类海绵体中一氧化氮能系统对去甲肾上腺素能系统的主导地位也表明这种相互作用在勃起功能障碍的病理生理学中起关键作用。事实上，在勃起功能障碍患者的阴茎组织中，已发现有利于去甲肾上腺素能系统的一氧化氮能 - 去甲肾上腺素能失衡。然而，这种失衡的机制尚未完全了解。此外，由于本研究表明5型磷酸二酯酶抑制剂可以增强并延长一氧化氮能对去甲肾上腺素能反应的控制，此类化合物在一氧化氮能传递缺陷伴有去甲肾上腺素能活性增加的阳痿治疗中可能具有治疗潜力。
