Reduced efficacy of nitrergic neurotransmission exacerbates erectile dysfunction after penile nerve injury despite axonal regeneration
Reduced efficacy of nitrergic neurotransmission exacerbates erectile dysfunction after penile nerve injury despite axonal regeneration
复制标题
DOI：
10.1016/j.expneurol.2007.05.011
复制
发表时间：
2007-09-01
影响因子：
5.3
通讯作者：
Keast, Janet R.
中科院分区：
文献类型：
--
作者：
Nangle, Matthew R.;Keast, Janet R.
在根治性前列腺切除术中，阴茎（海绵状）神经很容易受损，导致阳痿。勃起功能可以恢复，但这可能需要几个月或几年的时间，而且能力通常仍然很差。许多研究试图改善阴茎神经再生，但尚未探索功能恢复延迟的机制。这被认为是由于轴突生长缓慢，尽管阴茎组织也会随着勃起活动的丧失而发生变化。我们已经询问了氮能神经引起的勃起反应的延迟恢复是由于突触前（轴突生长缓慢）还是突触后（组织反应性改变）机制。这些成分在成年大鼠阴茎神经损伤后进行了体外解剖。两根阴茎神经挤压后，10-12周后氮能轴突再生良好，但空洞肌神经源性松弛仍相对较差。这至少部分是由于损伤后3周组织对一氧化氮（使用硝普钠作为供体）的反应性减弱。免疫印迹也显示可溶性胍基环化酶的适度减少。第二种阴茎神经损伤模型，单侧切断，一侧完全失神经，但保留阴茎勃起的潜力。一些解剖和功能在9-11周后恢复（可能是由于对侧未受伤的轴突发芽），但硝普肽诱发的松弛至少在3周后没有改变。这些数据表明，广泛神经损伤后的勃起功能障碍可能会因突触后一氧化氮信号的变化而加剧，即使神经再生发生。这可以通过持续激活阴茎组织来保持正常的灌注来防止。(c) 2007爱思唯尔公司版权所有。
Penile (cavernous) nerves are readily damaged during radical prostatectomy, invariably causing impotence. Erectile function can return, however this may take months or years and capacity often remains poor. Many studies have attempted to improve penile nerve regeneration but have not explored mechanisms underlying the delay in functional recovery. This is assumed to be due to slow growth of axons, although penile tissues also change following loss of erectile activity. We have asked whether delayed recovery of the nitrergic nerve-evoked erectile response is due to pre-synaptic (slow axonal growth) or post-synaptic (changes in tissue responsiveness) mechanisms. These components were dissected in vitro following penile nerve injury in adult rats. Following crush of both penile nerves, excellent regeneration of nitrergic axons occurred after 10-12 weeks but neurogenic relaxation of cavemosum muscle was still relatively poor. This was at least partly due to attenuated tissue responsiveness to nitric oxide (using sodium nitroprusside as a donor) from 3 weeks after injury. Western blotting also revealed a modest reduction of soluble guanylyl cyclase. A second model of penile nerve injury, unilateral cut, completely denervated one side but retained potential for penile erection. Some anatomical and functional recovery occurred after 9-11 weeks (probably due to sprouting from contralateral uninjured axons), but nitroprusside-evoked relaxations were unaltered from at least 3 weeks onward. These data suggest that erectile dysfunction following extensive nerve injury may be exacerbated by postsynaptic changes in nitric oxide signaling, even when nerve regeneration occurs. This may be prevented by continued activation of penile tissues to retain normal perfusion. (c) 2007 Elsevier Inc. All rights reserved.