勃起功能障碍与心血管疾病的关系

随着人口步入老龄化,高血压、冠心病等心血管危险因素逐年增加,心血管疾病与勃起功能障碍(erectile dysfunction,ED)之间的关系越来越受到重视.本文简要综述了两者关系及心血管疾病患者ED的治疗进展.一、ED与心血管疾病关系(一)ED和心血管疾病有共同的危险因子心血管疾病的诸多危险因素(老年、吸烟、糖尿病、脂代谢紊乱、肥胖和少活动等)也是ED的危险因子.1.老年:目前普遍认为ED是一个与年龄相关性疾病.多个流行病学调查均表明ED的患病率随着年龄的增长逐渐增高.患病率可从20岁的0.1％到80岁的75％.北京地区老年男性性生活平均终止年龄及ED的发生率及影响因素的调查研究显示,北京地区男性终止性生活(2年以上无性交)年龄为(68.4±5.2)岁,ED发病率为89.4％,其中轻度6.7％、中度18.6％、重度28.4％和无性生活率35.7％.在严重ED终止性生活的老年男性中,60～64岁组占26.8％,而70岁以上组则超过50％[1].     

低氧与勃起功能障碍的关系

勃起功能障碍(erectile dysfunction,ED)与低氧关系密切。正常人阴茎处于疲软状态时,海绵体小梁间隙氧分压(PO2)为20～40mmHg;而阴茎勃起时,其PO2增至90～100mmHg,达到动脉血水平     

细胞凋亡与男性勃起功能障碍

勃起功能障碍(ED)是男性,尤其是老年男性的常见病和多发病。目前,对于引起ED的机制了解尚不深入。越来越多的研究发现勃起组织的过度凋亡是引起ED的重要机制之一。多数ED的危险因素均可以引起阴茎勃起组织的过度凋亡,从而影响勃起功能。本文就细胞凋亡的机制、凋亡在ED中的作用及凋亡与ED的危险因素糖尿病、高脂血症、海绵体神经损伤和衰老之间的关系作一综述。     

性传播疾病与勃起功能障碍

目的探讨勃起功能障碍（ED）与性传播疾病（STD）的关系。方法回顾性分析我院1995年1月至2005年1月4521例男性STD患者的临床资料，对发生ED患者的治疗前后情况进行比较并分析ED成因。结果治疗前3259例（72．1％）STD患者发生ED，STD高发年龄段在20-40岁，ED的严重程度与患者的年龄、病史、精神压力、并发症有密切关系（P〈0．01）。有357例ED患者的疗效不佳。结论STD患者长期未接受规范治疗，可能由于临床症状加重和心理因素共同作用引起ED；STD痊愈后，绝大多数患者的ED症状消失，但有部分患者由于心理或器质性原因，ED未得到明显改善。     

内皮细胞凋亡与勃起功能障碍的研究进展

勃起功能障碍(ED)是泌尿男科最常见的疾病之一,严重影响患者的生活质量,引起ED的因素包括衰老、糖尿病、高血压、高脂血症以及不良生活方式等,其确切机制尚未完全明确。目前随着对ED研究的不断深入,其中阴茎海绵体内皮细胞凋亡与ED的关系倍受关注,内皮细胞凋亡增加可引起NOS活性降低导致NO合成受阻,从而影响阴茎勃起,不同病因引起的ED其内皮细胞凋亡的机制不同。本文就阴茎海绵体内皮细胞凋亡在ED中的作用作一综述,对ED与内皮细胞凋亡机制的深入了解将为新药研制及其他治疗措施提供新的思路。     

勃起功能障碍的基础研究进展

阴茎勃起是在一系列正常的神经、内分泌调节下的血管性生物活动.在正常性刺激下,神经信号通过阴茎海绵体内副交感神经,非肾上腺、非胆碱能神经传导至阴茎末梢,释放诱发阴茎勃起的生物活性因子,使阴茎动脉扩张,海绵体平滑肌松弛,海绵体窦的膨胀使阴茎体积增大.     

雄激素缺乏与勃起功能障碍

雄激素可通过增强性欲、性唤起等间接促进阴茎勃起,在维持阴茎正常的勃起组织结构方面起重要作用。睾酮缺乏可导致小梁平滑肌减少、细胞外基质增多、白膜下脂肪细胞沉积等。勃起时,阴茎组织的上述改变可引起静脉闭塞不全而发生静脉漏,从而出现勃起功能障碍;睾酮还可影响一氧化氮合酶(NOS)、RhoA/Rho激酶的表达及活性从而直接影响阴茎勃起。对单用磷酸二酯酶5(PDE5)抑制剂无反应的性腺功能减退的ED患者补充睾酮可收到良好的治疗效果。     

勃起功能障碍的治疗进展

勃起功能障碍（Erectiledysfunction,ED）的治疗方式在近10年获得了飞速的进展,从磷酸二酯酶抑制剂（PDE-5i）的临床广泛应用,新型PDE-5i的市场准入,到阴茎假体的临床应用.从基因治疗到目前热门的干细胞治疗勃起功能障碍的理论提出及治疗方式的初步尝试,为ED的治疗提供了新的研究方向.随着分子生物学对ED病因和形成机制研究的深入,转基因治疗在不久的将来会成为治愈ED最有效的方法之一.     

勃起功能障碍治疗新动向

WHO指出 ,人类健康应包括躯体、心理和社会文化的总体健康。现代健康新概念使性与生殖健康在总体健康中的地位显得更为重要。最近一项涉及全球 2 8个国家和地区约 2 60 0 0份的调查结果显示 ,超过 80 %的男性和 60 %的女性认为性生活是他们整个生活中的重要组成部分。勃起功能障碍 (ED)是男子最常见的性功能障碍 ,虽不致命 ,但使人生活质量下降。一直以来 ,ED是患者难以启齿 ,而事实上又难以治愈的疾病。上世纪末西地那非地问世是ED治疗史上重要的里程碑 ,使许多患者敢于启齿去寻找医疗帮助 ,同时进一步推动了治疗ED药物的开发 ,使ED…     

香烟烟雾与勃起功能障碍

勃起功能障碍是目前影响男性性健康最主要的原因,吸烟和动脉硬化、糖尿病、高血压一样,是公认的器质性勃起功能障碍的危险因子。吸烟可使勃起组织发生氧化应急损伤,勃起介质释放紊乱,海绵体血流动力学发生改变,雄激素合成减少,从而影响阴茎勃起功能。关于吸烟与勃起功能障碍的基础性研究已取得部分成果,但仍有许多问题尚未得到阐明,对这些问题的研究都将是一个全新的研究领域。     

Local control of penile erection. Nerves, smooth muscle, and endothelium

This article reviews the state of knowledge on the neurologic and non-neurologic mechanisms that control the tone of the corpus cavernosum trabecular smooth muscle and the smooth muscles of penile arteries and veins. It includes discussion of the role of the adrenergic, the cholinergic, and the nonadrenergic noncholinergic neuroeffector systems as well as the potential role of the vascular endothelium and prostaglandins in the control of penile erection.     

Intracellular mechanism of penile erection in monkeys

To elucidate the sequence of events between the release of neurotransmitters and cavernous smooth muscle relaxation in erection, we studied the role of the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) systems. In a well-established simian model, the effects of specific agonists and antagonists of the intracellular sequence for smooth muscle relaxation and potassium channel openers on the intracavernous pressure were examined. Sodium nitroprusside (10^?3 M), a nitric oxide releaser and thus a stimulant of the cGMP system, caused an increase in the intracavernous pressure from 82 to 115 cm H₂O for 7 to 19 min and penile diameter from 24.8 ± 2.28 to 43 ± 4.87 mm. When nitroprusside was injected after methylene blue (10^?3 M), a specific antagonist of the enzyme guanylate cyclase, intracavernous pressure rise decreased significantly, but cromakalin, a potassium channel opener, provoked excellent increases after the block. A smaller dose of sodium nitroprusside (10^?4 M) caused an increase in intracavernous pressure from 35 to 85 cm H₂O for 7 to 11.5 min. When nitroprusside was injected after zaprinast, a phosphodiesterase inhibitor, the increase in pressure ranged from 80 to 116 cm H₂O for 15 to 30 min. Prostaglandin E₁, an activator of the cAMP system, caused an increase in the intracavernous pressure of 20–80 cm H₂O for 5 to 10 min, and an increase in penile diameter from 25 ± 2.22 to 35 ± 3.48 mm. The erectile response to PGE₁, but not to cromakalin, was nearly abolished by ethylmaleimide, an adenylate cyclase blocker. The response to nitroprusside was significantly greater (P < 0.05) than to PGE₁. Both systems. cAMP and cGMP, may be involved in cavernous smooth muscle relaxation, and cGMP is probably the predominant intracellular second messenger in penile erection in monkeys. Stimulants of the cGMP system, such as nitric oxide releasers, could represent a more physiological and effective approach in the treatment of erectile dysfunction. © 1994 Wiley-Liss, Inc.     

The effect of DA-8159 on corpus cavernosal smooth muscle relaxation and penile erection in diabetic rabbits

A previous study showed that DA-8159, a potent type 5 phosphodiesterase inhibitor, enhanced the relaxation of the smooth muscles in the normal rabbit corpus cavernosum. In this study, we investigated the in vitro effects of DA-8159 on cavernosal smooth muscle relaxation and the in vivo erectogenic potential in diabetic rabbits, since erectile dysfunction is a well-known sequela of diabetes mellitus. Diabetes mellitus was induced in male New Zealand White rabbits with alloxan monohydrate. Cavernosal strips from age-matched control and 8-week diabetic animals were mounted in organ baths. The relaxation responses to sodium nitroprusside (10^-910^-5 M), a nitric oxide donor, were assessed in the presence or absence of DA-8159 (10^-910^-6 M). For the penile erection test, DA-8159 was given orally (1~10 mg/kg) to diabetic rabbits and the length of the uncovered penile shaft was measured in a time-course manner in the presence or absence of intravenous sodium nitroprusside. The sodium nitroprusside-stimulated relaxations were significantly impaired in the corpus cavernosum from the diabetic group (IC₅₀=1.07×10^-6 M following 8 weeks of diabetes mellitus; compared with 0.48×10^-6 M for age-matched controls). DA-8159 significantly and dose-dependently enhanced the sodium nitroprusside-stimulated relaxation in the diabetic groups. In addition, DA-8159 induced a dose-dependent penile erection in diabetic rabbits, which was potentiated by intravenous sodium nitroprusside. These results suggest that DA-8159 is an effective treatment for diabetic erectile dysfunction but further evaluation of the efficacy on human needs to be performed.     

Transdifferentiation of rat fetal brain stem cells into penile smooth muscle cells

OBJECTIVES

To evaluate whether rat fetal brain stem cells can be induced to acquire cell fates outside the nervous system, hypothesising that cell‐based replacement therapy with stem cells can aid in the regeneration of penile smooth musculature and might help to attenuate organic erectile dysfunction (ED), as the degeneration of penile smooth muscle cells leading to subsequent impairment of function is important in organic ED.

MATERIALS AND METHODS

Fetal brain stem cells (FBSCs) from embryonal 12‐day Fisher 344 rats were isolated and characterized. For in vitro studies, undifferentiated FBSCs were cultured for 21 days in either N2 media (control) or N2 media conditioned in rat penile smooth muscle cell culture. These were then subjected to immunocytochemistry for specific markers of neural stem cells (nestin) and penile smooth muscle cells, i.e. α‐smooth muscle actin (αSMA), penis‐specific myosin light chain (MLC) desmin, calponin, vimentin, phosphodiesterase‐5 (PDE5) and connexin. For in vivo studies, male adult Fisher 344 rats had an intracavernous injection with saline (five rats, control) or FBSCs that were labelled genetically by an expression construct for green fluorescent protein (GFP, nine rats, experimental) and maintained for 6 weeks. The rats were then killed and penile tissue was harvested and subjected to immunocytochemistry for markers of neural stem cells, smooth muscle cells, and sinusoidal endothelium (vascular endothelial growth factor, VEGF).

RESULTS

Undifferentiated cells exposed to N2 media continued to maintain the characteristic morphological and protein marker features of FBSCs, while the cells exposed to the conditioned media acquired the morphological features of smooth muscle cells. In addition, the differentiated cells (30–40%) expressed smooth muscle markers. Rats implanted with FBSCs had cells that showed double‐labelling for GFP/αSMA, GFP/calponin and GFP/VEGF. The control group had no evidence of such double‐labelling.

CONCLUSIONS

These results suggest the transdifferentiation of FBSCs into penile smooth muscle cells. Such transdifferentiated cells showed long‐term survival when injected into the cavernous tissue, thus raising the possibility of a novel therapeutic option for organic ED.     

Electrostimulation and penile erection

Electrostimulation was used to study the neuroanatomy and physiology of penile erection in dogs and monkeys. The canine spinal nuclei responsible for penile erection, identified by the retrograde horseradish peroxidase transport technique after verification of the cavernous nerves with neurostimulation, were mediolateral autonomic neurons at T12-L3 and S1-S3. The erection induced by electrostimulation of the cavernous nerves is the result of increased arterial flow, relaxation of cavernous muscles, and venous outflow restriction. Study of electrostimulation in dogs and monkeys is invaluable for the understanding of the complex neurophysiology of human penile erection.     

Thalamus and penile erection

Penile erection is a complex neurovascular event. The neuronal system involved is often divided into a spinal (generator) and supraspinal (controller) network. Little is known about the supraspinal control. The recent finding of changes in penile erection following deep brain stimulation of the thalamus in two patients has raised the question as to what extent the thalamus is involved in erectile function. The thalamus has generally been regarded as a group of relay nuclei that served as a 'gate' for sexual information from the spinal cord towards higher centres. Recent evidence, however, suggests a more integrated regulatory function. Our review of the literature from 1960 until 2003 revealed 13 reports describing original data (preclinical and clinical). Various thalamic regions, varying from the midline thalamus to the posterior thalamus, have been reported to be activated during erection. The majority of the reports, however, showed that mainly the mediodorsal (MD) nucleus and the centromedian-parafascicular nucleus (Cm-Pf complex) are involved in penile erection. MD is the second largest nuclear aggregation located within the medial part of the thalamus. Anatomically, the MD is closely related to the Cm-Pf complex. The Cm-Pf complex is one of the most important relay stations in which the anterolateral spinothalamic pathway is further processed. This pathway is thought to transmit peripheral sexual sensations. On the whole, the present data on the role of the thalamus in erection are far from complete and future experiments are required to delineate its involvement.     

The physiology of penile erection. I. Hemodynamics of penile erection

Arterial and venous flow and pressure studies of the corpora cavernosa were performed to elucidate the hemodynamics of canine penile erection. Being able to induce erection by electrical stimulation we were able to study the functionally relevant parameters at different stages of penile erection. From our results we conclude that penile erection can be subdivided in 5 phases: (1) latent-, (2) tumescence-, (3) erection-, (4) rigidity- and (5) detumescence phase. Furthermore, a differentiation of these subdivisions is made by observing at the mechanism of the 5 different stages: phase 1 to 4 is an active phenomenon, the detumescence phase is passive only.     

Contraction of smooth muscle in Ca-free solution

The tonic contractions which are extremely resistant to removal of the external Ca were investigated in the rat vas deferens and myometrium. Both the noradrenaline response in the vas deferens and the oxytocin response in the myometrium could be repeatedly produced without appreciable diminution in Ca-free solution for more than 24 hrs. On the other hand, the tissue Ca content decreased exponentially after Ca-removal with a half time of 130-180 min. When Ca was readmitted, no indication of the early transient contraction was observed in the subsequent response in Ca-free solution, but the response was reduced compared with the response before Ca readmission. Verapamil suppressed the response in the presence of Ca, while it had very weak inhibitory effect even at 10 microM. Calmodulin antagonists of phenothiazine derivatives had a strong inhibitory effect on Ca-induced contractions, whereas they had very weak effects on the receptor-mediated contraction in Ca-free solution. Another calmodulin antagonist, W-7 suppressed both Ca-induced contraction and the contractions independent of external Ca. HA-1004, a vasodilator which has a structure similar to W-7, reduced the receptor-mediated contraction in Ca-free solution without much effect on Ca-induced contractions. These results may suggest that the receptor-mediated contractions resistant to Ca-removal are caused by some process without a contribution of the Ca-calmodulin system.     

Hemodynamics of penile erection

In the flaccid state, the smooth muscles of the cavernous arterioles and trabeculae are contracted, and minimal blood flow enters the sinusoids. Relaxation of these smooth muscles incites arterial dilation, venous compression, and sinusoidal relaxation and results in penile erection.