Plasma levels of endothelin-1, angiotensin II, nitric oxide and prostaglandin E in the venous and cavernosal blood of patients with erectile dysfunction

OBJECTIVES: To determine the alterations in the plasma levels of endothelin-1, angiotensin II, nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in the venous and cavernosal blood of patients with organic and psychogenic erectile dysfunction (ED). PATIENTS, SUBJECTS AND METHODS: The study included 32 patients complaining of ED; they were subdivided into two equal groups with either organic or psychogenic ED. Fifteen healthy potent age-matched male volunteers were enrolled as a control group. For each patient, venous and cavernosal blood samples were obtained, while venous blood was obtained from the controls. RESULTS: There were significantly greater mean plasma levels of endothelin-1 and angiotensin II, and significantly lower mean plasma levels of NO and PGE(2), in the venous blood of patients with ED than in the controls. Patients with organic ED had significantly higher levels of endothelin-1 and significantly lower levels of NO in both venous and cavernosal blood than had those with psychogenic ED. There were significant positive correlations in both venous and cavernosal blood between endothelin-1 and angiotensin II, and between NO and PGE(2) in all patients with ED and the two subgroups. There were significant negative correlations between venous and cavernosal endothelin-1 and NO, endothelin-1 and PGE(2), angiotensin II and NO, and between angiotensin II and PGE(2). CONCLUSION: The present results suggest that endothelin-1 could be a clinical marker of diffuse endothelial disease manifested by ED. As angiotensin-converting enzyme (ACE) activity controls angiotensin II there might be a rationale for the use of ACE inhibitors to prevent or treat ED. NO and PGE(2) may provide new strategies for the pharmacological treatment of ED.     

Cavernosal tissue nitrite,nitrate, malondialdehyde and glutathione levels in diabetic and non-diabetic erectile dysfunction

The aim of this study is to investigate the role of nitric oxide (NO) stabile end products, membrane lipid peroxidation and antioxidant defensive mechanism in diabetic erectile dysfunction (ED) and compare these parameters with non-diabetic ED groups. We examined the penile cavernosal tissues, obtained from 22 patients who had undergone surgery of penile prostheses implantation, for the nitrite, nitrate, malondialdehyde (MDA) and glutathione (GSH) levels. Eight patients were suffering from diabetic erectile dysfunction (ED) and 14 patients had non-diabetic ED. Nitrite and nitrate levels were lower; MDA and GSH levels were higher in the diabetic group. There were statistically significant differences between diabetic and non-diabetic groups amongst the nitrite (p<0.001), nitrate (p<0.01), MDA (p<0.001) and GSH (p<0.01) levels. Our data provide evidence that NO deficiency, possibly due to the membrane lipid peroxidation and defective antioxidant defensive mechanism, may contribute to the development of diabetic ED and thus is involved in the pathogenesis of ED in diabetic patients.     

螺旋CT对动脉性勃起功能障碍诊断的应用分析

目的探讨初步运用螺旋CT对动脉性勃起功能障碍（ED）诊断的价值。方法对9例临床拟诊为动脉性ED的患者行螺旋CT增强扫描，运用螺旋CT原始图像，结合CT三维软件后处理进行观察诊断。结果观察组9例中，2例阴茎背动脉中断，6例有不同程度阴茎深动脉狭窄和充盈欠佳，1例表现为单侧阴部内动脉充盈缺损。结论运用螺旋CT对动脉性ED可以进行初步筛查性诊断。     

Roles of nitric oxide, malondialdehyde, and fibronectin in an experimental peripheral nerve ischemia-reperfusion model

Although there are many studies of the neuropathology of the ischemic degeneration of peripheral nerves, the pathogenesis is not well-understood. The roles of several biomolecules on this process were previously reported. An adhesion molecule, fibronectin, which is applied locally (as a conduit material), is very effective in nerve recovery. This study was carried out to evaluate the roles of fibronectin, lipid peroxidation, and nitric oxide (NO) in an experimental model of peripheral nerves. Ischemia and reperfusion injury of sciatic nerves was rendered by clamping the femoral artery and vein. Rats were divided into nine groups. Ischemia and reperfusion were not applied to group 1. In group 2, only ischemia was performed, but reperfusion was not accomplished. For groups 3-9, 1, 2, and 24 h and 1, 2, 3, and 4 weeks of reperfusion were applied following 3 h of ischemia. Then NO, malondialdehyde (MDA), and fibronectin levels were observed in serum samples of rats. Colorimetric and nephelometric assays were used for determination of the levels of these parameters. In this study, all biochemical parameters were found to be increased in the ischemia groups when compared with the control group 1 (P < 0.05). A significant difference was observed between study groups with respect to MDA, NO, and fibronectin levels (P < 0.05). Also, some correlations were established between biochemical parameters in the same group, depending on the varying reperfusion time (r > 0.50). Ischemia causes some important changes in biochemical parameters, and depending on the reperfusion time, nerve injury continues for a while. In our study, we observed that serum levels of MDA decreased in the periods when NO and fibronectin simultaneously increased. Such increases may contribute to neural recovery, and there may be interactions among them.     

The value of testing pudendal nerve conduction in evaluating erectile dysfunction in diabetics

We conducted an open prospective study on the value of testing pudendal nerve conduction (PNC) in 45 diabetic and 32 nondiabetic men with documented erectile dysfunction (ED) of at least six months duration. All subjects underwent PNC by the same investigator using the Medcelec/TECA Sapphire device with calibration parameters of sweep 10 ms/div an amplitude of 200 microV/div. No statistically significant differences was found in the mean bulbocavernosus reflex (BCR) latencies between the nondiabetics (33.6 ms/div +/- 4.1) and the diabetics (37.5 ms/div +/- 9.1) (P > 0.05). Our results show that electrophysiological measurement of the BCR in diabetics is not a useful diagnostic test and emphasize the importance of a multifactorial evaluation of diabetic ED.     

糖尿病性阴茎勃起功能障碍大鼠阴茎海绵体一氧化氮合酶活性的测定

目的　探讨糖尿病 (DM )性阴茎勃起功能障碍 (ED)的发病机理。　方法　SD大鼠注射链脲佐菌素建立DM动物模型后 ,注射阿朴吗啡观察 6周、8周及 12周大鼠阻茎勃起情况 ,筛选DM性ED大鼠模型 ,测定其阴茎海绵体组织一氧化氮合酶 (NOS)的活性。　结果　DM性ED大鼠阴茎海绵体组织NOS活性与对照组相比显著降低 (P <0 0 0 1或P <0 0 1) ,随DM病程延长 ,NOS活性明显下降 (P <0 0 1)。　结论　DM严重影响阴茎勃起功能 ,海绵体组织NOS活性降低可能是其发病机理之一。     

Rehabilitation of the cavernous smooth muscle in patients with organic erectile dysfunction

This study aimed at assessing the effect of regular use of intracorporeal injection (ICI), sildenafil citrate and vacuum constriction device (VCD) on cavernous smooth muscle and erectile activity. One hundred and sixty-five patients with organic erectile dysfunction were investigated for 3 months. The patient and his partner were classified prospectively after proper counselling: group I (n = 56) received ICI twice per week; group II (n = 55) received sildenafil 100 mg twice per week; and group III (n = 54) used VCD twice per week. Duplex ultrasound was carried out before and after treatment, and then, the patients were followed up for a month to assess the resumption of unaided erection. The results showed that there was significant improvement in mean peak systolic velocity (PSV) and mean cavernosal artery diameter (CAD) at the end of the treatment in all groups, being higher in the ICI group than in the other two groups. Also, the percentage of patients who resumed unaided intercourse were higher in the ICI group compared with the other two groups (17.9%, 9.1% and 3.7% respectively). It is concluded that repeated regular use of ICI, sildenafil or VCD by patients with organic erectile dysfunction has a positive impact on their cavernous blood flow and erectile activity.     

Preliminary results with the nitric oxide donor linsidomine chlorhydrate in the treatment of human erectile dysfunction.

Recent experimental studies showed an important role of endothelium derived relaxing factor for cavernous smooth muscle relaxation. Since nitric oxide seems to account for the biological actions of endothelium derived relaxing factor, a study was done to examine a possible role of the nitric oxide donor linsidomine chlorhydrate (SIN-1) in the treatment of erectile dysfunction. To determine a therapeutically useful dose 0.1, 0.2, 0.5 and 1 mg. SIN-1 were injected intracavernously in patients with erectile dysfunction. Each dose was given to 2 patients. Then, 63 patients received 1 mg. SIN-1, including 7 who had prolonged erections to minimal doses of papaverine plus phentolamine and 4 who did not respond with a full erection to other pharmacological agents. Intracavernous injection of SIN-1 induced a dose-dependent erectile response by increasing the arterial inflow and relaxing cavernous smooth muscles. Of the patients 29 had a full, 21 an almost full and 13 a moderate erection to 1 mg. SIN-1. There were no systemic or local side effects. In the patients with prolonged erections to papaverine plus phentolamine the mean duration of a full erectile response to SIN-1 was 57 minutes. Compared to the responses to a papaverine (15 mg./ml.) and phentolamine (0.5 mg./ml.) mixture, the erection induced by SIN-1 was superior in 10, comparable in 47 and inferior in 6 patients. Our data suggest a possible role for SIN-1 in the treatment of erectile dysfunction. Possible advantages may be that erection is induced by a mechanism similar to that occurring physiologically, a decreased risk of inducing prolonged erections and low therapy costs.     

Diagnostic steps in the evaluation of patients with erectile dysfunction

PURPOSE: The necessity for a thorough diagnostic evaluation for erectile dysfunction has been questioned after the availability of effective oral therapies. We determined the impact of the different diagnostic steps on the management strategy for erectile dysfunction. MATERIALS AND METHODS: The study included all patients who presented at an andrology outpatient clinic during a 4-year period. Baseline evaluation included medical and sexual history, blood tests, physical examination and intracavernous injection test. Patients with normal initial screening were evaluated with specific diagnostic procedures. The results were analyzed to identify the diagnostic potential of each screening step separately. RESULTS: Overall 1,644 patients presented at the clinic during the study period, of whom 368 (22.4%) were excluded from study due to severe psychiatric (5.2%) or cardiovascular (2.7%) disease, or to a history of erectile dysfunction less than 3 months in duration (14.5%). In the remaining 1,276 patients with a mean age plus or minus standard deviation of 56 +/- 14 years, and a mean duration of erectile dysfunction of 4.9 +/- 3.4 years medical history revealed erectile dysfunction associated medical conditions in 57%, blood tests identified previously undiagnosed medical conditions in 6.2%, and physical examination and the intracavernous injection test were diagnostic in 13.9% and 2.6%, respectively. Initial screening was negative in 259 cases (20.3%), in which specific diagnostic procedures identified an underlying vascular pathology in 165 (12.9%) and unfavorable penile geometry in 16 (1.3%). The remaining 78 men (6.1%) had no evidence of organic disease. CONCLUSIONS: Baseline diagnostic evaluation for erectile dysfunction can identify the underlying pathological condition or erectile dysfunction associated risk factors in 80% of patients. Such screening may diagnose reversible causes of erectile dysfunction and also unmask medical conditions that manifest with erectile dysfunction as the first symptom. Specific diagnostic procedures may be limited in patients with primary erectile dysfunction or those without risk factors. Such clinical data support previously published guidelines for erectile dysfunction management.     

Gene-polymorphisms of angiotensin converting enzyme and endothelial nitric oxide synthase in patients with erectile dysfunction.

AIMS OF THE STUDY: Regulation of the penile smooth muscle tone and contractility is closely related to the activity of vasoactive substances, angiotensin II or nitric oxide. We investigated the relationship between gene polymorphism in the angiotensin converting enzyme (ACE) or endothelial nitric oxide synthase (ecNOS) and development of erectile dysfunction. METHODS: In 84 subjects with organic erectile dysfunction and 63 control subjects, gene polymorphisms in the ACE and ecNOS were determined by the polymerase chain reaction (PCR). RESULTS: The DD genotype of ACE was significantly (P < 0.01) more frequent in subjects with organic erectile dysfunction (54%) than in control subjects (24%). There was no significant difference in the distribution of the genotypes of ecNOS. CONCLUSION: The deletion polymorphism in the ACE gene, the DD genotype, as a marker of general vascular disease, may be seen more frequently in men with a diagnosis of vasculogenic erectile dysfunction.     

Inhibition of inducible nitric oxide synthase improved erectile dysfunction in rats with type 1 diabetes

Diabetes mellitus (DM), which is closely related to microvascular dysfunction, is a risk factor for erectile dysfunction (ED). Furthermore, the upregulation of inducible nitric oxide synthase (iNOS) is associated with systemic vascular dysfunction in rats with diabetes. The purpose of this study was to investigate the role of iNOS in diabetes mellitus erectile dysfunction (DMED). First, we developed a type 1 DM rat model using streptozotocin and selected those that developed DMED. Then, we injected these rats with the 1400W, an iNOS inhibitor, for 10 weeks and subsequently assessed their ED. Lastly, we performed various molecular studies and histopathological analyses of penile tissues collected from these rats after the experiments. Through the histopathological studies, we also found that the treatment restored the ratios of the smooth muscle to collagen fibres, delayed the development of microvascular injury and alleviated the oxidative stress caused by hyperglycaemia. Based on these results, we confirmed that upregulation of iNOS leads to microvascular dysfunction in patients with ED. Overall, we found that inhibition of iNOS displayed beneficial effects in the treatment of ED, suggesting that its mechanism should be further explored.     

Significance of nitric oxide and its modulation mechanisms by endogenous nitric oxide synthase inhibitors and arginase in the micturition disorders and erectile dysfunction

Abstract:   Evidence indicates that nitric oxide (NO) deficiency contributes to micturition disorders, especially in the afferent pathway and erectile dysfunction (ED). Two possible causes of NO deficiency are substrate ( l -arginine) limitation and increased levels of endogenous inhibitors of NO synthase (particularly asymmetric dimethylarginine: ADMA) in plasma and tissues. Elevated tissues of ADMA and N^G-monomethyl-L-arginine (L-NMMA) have been reported to be associated with impaired NO-mediated urethral, trigonal and cavernosal relaxations by pelvic ischemia. Also, plasma ADMA may help to identify underlying cardiovascular disease in men with ED. Decreased l -arginine availability to NO synthase is due to the shunting of l -arginine into other pathways such as arginase. Interaction between NO synthase and arginase has been reported to be involved in NO-mediated urethral and prostatic relaxations. Also, increased arginase activity in cavernosal tissues likely contributes to the ED that accompanies diabetes mellitus and aging. Therefore, arginase inhibition has been reported to enhance the NO-dependent physiological process for erectile function.     

Histopathological changes and nitric oxide synthase activity in corpus cavernosum from rats with neurogenic erectile dysfunction

OBJECTIVE: To investigate changes in histology and nitric oxide synthase (NOS) activity in cavernosal tissues from rats with neurogenic erectile dysfunction induced experimentally. MATERIALS AND METHODS: Twenty-four adult male Sprague-Dawley rats were divided equally into three groups and underwent a sham operation (control, group 1), unilateral (group 2) or bilateral (group 3) cavernosal nerve resection. Three months later they were killed and the cavernosal tissues analysed histologically by light and transmission electron microscopy, with NOS activity detected using an NADPH-diaphorase staining technique. RESULTS: On light and electron microscopy, while penile nerves and cavernosal smooth muscle cells had a normal morphological appearance in the eight control rats, there were degenerative changes of the myelinated penile nerves and axonal fibrosis in groups 2 and 3. However, these changes were not significant. Using NADPH-diaphorase staining, NOS activity was detected in all three groups in endothelial cells and cavernosal structures. However, the staining was more intense in endothelial cells and cavernosal muscles of rats in group 2 than in the other groups. CONCLUSION: NOS activity was increased in the cavernosal tissue after cavernosal denervation, but the pharmacological action of nitric oxide may be impaired.     

静脉性勃起功能障碍诊疗的研究进展

静脉性勃起功能障碍(VED)在勃起功能障碍(ED)患者中占大部分,在临床中常常合并其他类型ED而被忽视,生活方式、精神因素、心血管疾病、糖尿病等均可导致VED。如今对静脉性勃起功能障碍的机制研究进一步明确,所以在其诊疗方面就有了许多创新和发展。本文将静脉性ED现有诊疗研究进行综述,为大家对静脉性ED的诊断和治疗提供参考。     

超声造影技术在静脉性勃起功能障碍诊断中的应用

目的:探讨超声造影技术用于静脉性ED诊断的有效性及安全性。方法:2015年6月至2016年3月在南京鼓楼医院泌尿男科通过阴茎海绵体造影确诊为阴茎海绵体静脉漏患者23例、无阴茎海绵体静脉漏患者20例,43例患者行阴茎海绵体活性药物注射+超声造影检查。结果:23例阴茎海绵体静脉漏患者中21例在超声造影过程中显示明显静脉漏,准确率为91.3%;其中双静脉漏型12例,单静脉漏型2例,阴茎脚静脉漏型5例,海绵体混合型静脉漏2例。2例超声造影未见静脉漏,与阴茎海绵体造影结果不相符。20例无阴茎海绵体静脉漏患者2例超声造影见静脉漏,与阴茎海绵体造影结果不相符。结论:超声造影技术诊断静脉性ED具有一定准确性;超声造影技术用于静脉性ED的诊断具有创伤小,安全性高等优点。