Argonaute 2 restored erectile function and corpus cavernosum mitochondrial function by reducing apoptosis in a mouse model of cavernous nerve injury.

PURPOSE: To determine whether the overexpression of the Argonaute RNA-induced silencing complex catalytic component 2 (Ago2) improves erectile function in mice after cavernous nerve injury (CNI). MATERIALS AND METHODS: Lentiviruses containing Ago2 open reading frame (ORF) mouse clone (Ago2 O/E) were used to overexpress Ago2, and lentiviruses ORF negative control particles (NC) were used as a negative control. Three days before preparing the CNI model, we injected lentiviruses into the penises of 8-week-old male C57BL/6 mice. Animals were then divided into four groups: the sham operation control group and the CNI+phosphate-buffered saline, CNI+NC, and CNI+Ago2 O/E groups. One week later, erectile function was assessed by electrically stimulating cavernous nerves bilaterally and obtaining intracavernous pressure parameters. Penile tissue was also collected for molecular mechanism studies. RESULTS: Ago2 overexpression improved erectile function in mice after CNI-induced erectile dysfunction (ED). Immunofluorescence staining and Western blot analysis showed that under Ago2 overexpressing conditions, the contents of endothelial cells, pericytes, and neuronal cells increased in the penile tissues of CNI mice, and this was attributed to reduced apoptosis and ROS production. In addition, we also found that Ago2 overexpression could restore penile mitochondrial function, thereby improving erectile function in CNI-induced ED mice. CONCLUSIONS: Our findings demonstrate that Ago2 overexpression can reduce penile cell apoptosis, restore penile mitochondrial function, and improve erectile function in CNI-induced ED mice.

Krause corpuscles are genital vibrotactile sensors for sexual behaviours.

Krause corpuscles, which were discovered in the 1850s, are specialized sensory structures found within the genitalia and other mucocutaneous tissues1-4. The physiological properties and functions of Krause corpuscles have remained unclear since their discovery. Here we report the anatomical and physiological properties of Krause corpuscles of the mouse clitoris and penis and their roles in sexual behaviour. We observed a high density of Krause corpuscles in the clitoris compared with the penis. Using mouse genetic tools, we identified two distinct somatosensory neuron subtypes that innervate Krause corpuscles of both the clitoris and penis and project to a unique sensory terminal region of the spinal cord. In vivo electrophysiology and calcium imaging experiments showed that both Krause corpuscle afferent types are A-fibre rapid-adapting low-threshold mechanoreceptors, optimally tuned to dynamic, light-touch and mechanical vibrations (40-80 Hz) applied to the clitoris or penis. Functionally, selective optogenetic activation of Krause corpuscle afferent terminals evoked penile erection in male mice and vaginal contraction in female mice, while genetic ablation of Krause corpuscles impaired intromission and ejaculation of males and reduced sexual receptivity of females. Thus, Krause corpuscles of the clitoris and penis are highly sensitive mechanical vibration detectors that mediate sexually dimorphic mating behaviours.

Caveolin-1 scaffolding domain-derived peptide enhances erectile function by regulating oxidative stress, mitochondrial dysfunction, and apoptosis of corpus cavernosum smooth muscle cells in rats with cavernous nerve injury.

AIM: Increased corpus cavernosum smooth muscle cells (CCSMCs) apoptosis in the penis due to cavernous nerve injury (CNI) is a crucial contributor to erectile dysfunction (ED). Caveolin-1 scaffolding domain (CSD)-derived peptide has been found to exert potential antiapoptotic properties. However, whether CSD peptide can alleviate CCSMCs apoptosis and ED in CNI rats remains unknown. The study aimed to determine whether CSD peptide can improve bilateral CNI-induced ED (BCNI-ED) by enhancing the antiapoptotic processes of CCSMCs. MAIN METHODS: Fifteen 10-week-old male Sprague-Dawley (SD) rats were randomly classified into three groups: sham surgery (Sham) group and BCNI groups that underwent saline or CSD peptide treatment respectively. At 3 weeks postoperatively, erectile function was assessed and the penis tissue was histologically examined. Furthermore, an in vitro model of CCSMCs apoptosis was established using transforming growth factor-beta 1 (TGF-ß1) to investigate the mechanism of CSD peptide in treating BCNI-ED. KEY FINDINGS: In BCNI rats, CSD peptide significantly prevented ED and decreased oxidative stress, the Bax/Bcl-2 ratio, and the levels of caspase3. TGF-ß1-treated CCSMCs exhibited severe oxidative stress, mitochondrial dysfunction, and apoptosis. However, CSD peptide partially reversed these alterations. SIGNIFICANCE: Exogenous CSD peptide could improve BCNI-ED by inhibiting oxidative stress, the Bax/Bcl-2 ratio, and caspase3 expression in penile tissue. The underlying mechanism might involve the regulatory effects of CSD peptide on oxidative stress, mitochondrial dysfunction, and apoptosis of CCSMCs following CNI. This study highlights CSD peptide as an effective therapy for post-radical prostatectomy ED (pRP-ED).

MicroRNA-503-5p protects streptozotocin-induced erectile dysfunction in diabetic rats by downregulating SYDE2.

Plentiful studies have clarified miRNAs take on a key role in the sexual dysfunction of diabetic rats. This study aimed to figure out microRNA (miR)-503-5p/SYDE2 axis' latent mechanisms in streptozotocin-induced diabetic rat sexual dysfunction. A model of erectile dysfunction (ED) in diabetic rats was established by injecting streptozotocin. MiR-503-5p and SYDE2 in ED rats were altered by injection of miR-503-5p mimic or si/oe-SYDE2. The targeting link between miR-503-5p and SYDE2 was testified. ICP/MAP value was tested by pressure sensor; Penile capillary abundance was assessed; Penile cGMP and AGEs were detected; penile smooth muscle cell apoptosis was assessed; MiR-503-5p and SYDE2 were tested. In streptozotocin-induced ED rats, miR-503-5p was reduced and SYDE2 was elevated. Elevating miR-503-5p or silencing of SYDE2 can enhance penile erection rate, ICP/MAP value, capillary abundance, and cGMP but reduce AGEs and penile smooth muscle cell apoptosis rate in ED rats. Strengthening SYDE2 with elevating miR-503-5p turned around the accelerating effect of elevated miR-503-5p on penile erection in ED rats. SYDE2 was a downstream target gene of miR-503-5p. MiR-503-5p protects streptozotocin-induced sexual dysfunction in diabetic rats by targeting SYDE2.

Ejaculatory and erectile function outcomes following holmium laser enucleation of the prostate.

PURPOSE: Holmium laser enucleation of the prostate (HoLEP) is a surgical treatment option for benign prostatic hyperplasia (BPH). Many men develop retrograde ejaculation postprocedure, but there is conflicting evidence regarding sexual function outcomes post-HoLEP. We sought to examine significant variations in patient-reported erectile and ejaculatory function within 12 months post-HoLEP. MATERIALS AND METHODS: We conducted a retrospective study for patients who underwent HoLEP between Nov 2018 and Feb 2022. Of the reviewed patients, 277 patients met inclusion criteria and completed pre and postoperative questionnaires, which included the Male Sexual Health Questionnaire- Ejaculatory Dysfunction (MSHQ-EJD) and the International Index of Erectile Function/Sexual Health Inventory for Men (IIEF-5/SHIM). Surveys were provided to patients up to 12 months postprocedure. Demographics and comorbidities associated with sexual dysfunction were collected. Responses to each question were analyzed to detect sub-categorical variations in sexual function as the secondary objective. Data was analyzed by using a linear mixed model. RESULTS: There was a significant decline in total scores for the MSHQ-EJD (8.70 pre-HoLEP vs. 6.58 post HoLEP, p ≤ 0.001) including a significant decline (p < 0.005) in questions 1-3 which assess ejaculatory ability, strength, and volume. There was not a significant decline in question 4 which assesses bother (2.552 pre-HoLEP vs. 3.119 post-HoLEP, p = 0.526). There was not a significant decline in the IIEF-5/SHIM postoperatively (11.51 pre-HoLEP vs. 13.327 post-HoLEP, p = 0.498). CONCLUSIONS: Patients undergoing HoLEP do not experience a decline in erectile function. Patients do experience a decline in ejaculatory function but did not find this bothersome.

A novel reuptake inhibitor, IP2015, induces erection by increasing central dopamine and peripheral nitric oxide release.

BACKGROUND AND PURPOSE: An estimated 40% of patients with erectile dysfunction have a poor prognosis for improvement with currently available treatments. The present study investigated whether a newly developed monoamine transport inhibitor, IP2015, improves erectile function. EXPERIMENTAL APPROACH: We investigated the effects of IP2015 on monoamine uptake and binding, erectile function in rats and diabetic mice and the effect on corpus cavernosum contractility. KEY RESULTS: IP2015 inhibited the uptake of 5-HT, noradrenaline and dopamine by human monoamine transporters expressed in cells and in rat brain synaptosomes. Intracavernosal pressure measurement in anaesthetized rats revealed that IP2015 dose-dependently increased the number and the duration of spontaneous erections. Whereas pretreatment with the dopamine D2-like receptor antagonists, clozapine and (-)-sulpiride, or cutting the cavernosal nerve inhibited IP2015-induced erectile responses, the phosphodiesterase type 5 inhibitor sildenafil further enhanced the IP2015-mediated increase in intracavernosal pressure. IP2015 also increased the number of erections in type 2 diabetic db/db mice. Direct intracavernosal injection of IP2015 increased penile pressure, and in corpus cavernosum strips, IP2015 induced concentration-dependent relaxations. These relaxations were enhanced by sildenafil and blunted by endothelial cell removal, a nitric oxide synthase inhibitor, NG-nitro-l-arginine and a D1-like receptor antagonist, SCH23390. Quantitative polymerase chain reaction (qPCR) showed the expression of the dopamine transporter in the rat corpus cavernosum. CONCLUSION AND IMPLICATIONS: Our findings suggest that IP2015 stimulates erectile function by a central mechanism involving dopamine reuptake inhibition and direct NO-mediated relaxation of the erectile tissue. This novel multi-modal mechanism of action could offer a new treatment approach to erectile dysfunction.

Trends, safety, and efficacy of wearable male sexual devices.

INTRODUCTION: The prevalence of male sexual dysfunction (MSD) increases with age, with >50% of men aged >40 years reporting erectile dysfunction (ED). In recent years, wearable male sex devices (WMSDs) have been increasingly utilized by patients and recommended by sexual medicine clinicians. OBJECTIVES: This study seeks to investigate the safety and efficacy of products currently marketed for the treatment of MSD. METHODS: Available products for WMSDs were reviewed by analyzing product websites, forums, advertisements, and clinical recommendations. Qualitative comparisons were based on patient reviews, cost, and specific features. Investigatory evidence and Food and Drug Administration status were also reviewed. Additionally, Google Trends was used to determine the popularity of devices over time. RESULTS: Eight WMSDs for the treatment of MSD and enhancement of sexual pleasure were reviewed. Constriction bands, such as the Maintain Ring Loop, Eddie by Giddy, and Xialla, have shown significant benefits in clinical trials and were the most popular devices among patients. Smart devices can provide real-time feedback on erectile quality and/or sexual performance. Similar to the RigiScan, the Adam sensor provides feedback on erectile quality while monitoring changes in penile tumescence during sleep with additional analysis available through a mobile application. Neuromodulation devices such as the Morari Patch and vPatch/in2 Patch use electrical stimulation to delay ejaculation and improve sexual function. The FirmTech Performance Ring uses sensors to track the vital signs of erectile fitness with clinical trials ongoing. CONCLUSIONS: Overall, this review describes the available investigatory evidence for a range of WMSDs and highlights the potential benefits and limitations of these devices in treating MSD and enhancing sexual pleasure. Further research is needed to evaluate the effectiveness of these devices and to determine which ones may be the most suitable for individual patients.

Penile erection and cardiovascular function: effects and pathophysiology.

Penile erection (PE) is a hemodynamic event that results from a neuroendocrine process, and it is influenced by the cardiovascular status of the patient. However, it may also modulate an individual's cardiovascular events. The present study provides the mechanisms involved in the association of PE and cardiovascular function. Erection upsurges the cardiac rate, blood pressure, and oxygen uptake. Sex-enhancing strategies, such as phosphodiesterase inhibitors, alprostadil, and testosterone also promote vasodilatation and cardiac performance, thus preventing myocardial infarction. More so, drugs that are used in the treatment of hypertensive heart diseases (such as angiotensin system inhibitors and ß-blockers) facilitate vasodilatation and PE. These associations have been linked with nitric oxide- and testosterone-dependent enhancing effects on the vascular endothelium. In addition, impaired cardiovascular function may negatively impact PE; therefore, impaired PE may be a pointer to cardiovascular pathology. Hence, evaluation of the cardiovascular status of an individual with erectile dysfunction (ED) is essential. Also, employing strategies that are used in maintaining optimal cardiac function may be useful in the management of ED.

Erectile function preservation after radiotherapy using a dose-optimization approach on sexual structures for localized prostate cancer.

PURPOSE: Erectile function preservation is an important quality of life factor in patients treated for prostate cancer. A dose-optimization approach on sexual structures was developed and evaluated to limit erectile dysfunction after radiotherapy. MATERIALS AND METHODS: Twenty-three men with localized prostate cancer and no erectile dysfunction were enrolled in the study. All patients received a prescription dose between 76 and 78Gy. Computed tomography/magnetic resonance image registration was used to delineate the prostatic volume and the sexual structures: internal pudendal arteries (IPA), penile bulb and corpus cavernosum. Erectile function was evaluated using the 5-items International Index of Erectile Function (IIEF-5) score every 6 months during the 2 years after radiotherapy and once a year afterwards. No erectile dysfunction, mild erectile dysfunction and severe erectile dysfunction were defined if the IIEF-5 scores were 20-25, 17-19 and < 17, respectively. RESULTS: The mean follow-up was 4.5 years. The mean age of the patients was 66.3 years. At 2 years, 67% of the patients had no erectile dysfunction, 11% had mild erectile dysfunction and 22% had severe erectile dysfunction. No significant difference was found between the patients with and without erectile dysfunction (IIEF-5≥20 and IIEF-5<20, respectively) for any of the parameters: dosimetric values (internal pudendal arteries, penile bulb, corpus cavernosum), age, comorbidity and smoking status. The biochemical-relapse free survival was 100% at 2 years. CONCLUSION: This approach with dose-optimization on sexual structures for localized prostate cancer found excellent results on erectile function preservation after radiotherapy, with 78% of the patients with no or mild erectile dysfunction at 2 years.

A novel strategy to induce penile erection during penile doppler ultrasound: oral sildenafil administration plus alprostadil injection.

OBJECTIVES: To evaluate the efficacy of a novel approach to achieve the optimal penile erection during the penile doppler ultrasound (PDU) examination, which was oral sildenafil combined alprostadil injection. MATERIALS AND METHODS: A total of 60 ED patients were enrolled in our prospective study, and they were randomly assigned to two group with different PDU order. The approaches assisted the PDU included two models, mode A meaning injection of 15 µg alprostadil and model B meaning oral sildenafil 100 mg plus injection of 15 µg alprostadil. The PDU parameters were measured continuously before induced erection, and 5, 10, 15, 20, 25 min. RESULTS: Each group included 30 ED patients with similar clinical characteristics. After pooling the results together, the PSV, EDV, and RI were all improved significantly, when adding the oral sildenafil administration to assist PDU. Also, the clinical response of oral sildenafil administration plus alprostadil injection was better than that in alprostadil injection alone (p = 0.016). The arterial ED were decreased from 31.67% to 15.00% with the P value 0.031, and the mixed ED was also decreased statistically (23.33% vs 8.33%, p = 0.024). CONCLUSION: Oral sildenafil administration plus alprostadil injection could improve the diagnostic accuracy of PDU.

A non-latex condom has no influence on male physiological sexual arousal / Un condón sin látex no influye en la excitación sexual fisiológica masculina

Background/Objective: Men do not use external condoms for several reasons, which can result in public health problems. One of these is related to Condom-Associated Erectile Problems. This study aimed to examine the sexual arousal response of heterosexual men when using an external condom made of synthetic resin type AT-10. Method: A total of 82 Colombian young men (Mage = 23.17 years, SD = 3.04, age range = 18–30) participated in this experimental study. Two random groups (experimental and control; n = 41 each) were compared. The experimental group used condoms, whereas the control group did not. Fit and feel condom perceptions, initial erectile scores, age, and substance use were controlled for. Erection was measured while viewing a sexual video by using penile plethysmography and subjective arousal. Results: The results, obtained from comparing the experimental group (using pre-erection condoms) with the control group (not using condoms), revealed no significant difference in both subjective and physiological sexual arousal. This suggests that pre-erection condoms do not have an effect on the erectile response. Discussion: More research is needed in this area to provide treatment and clinical interventions or sexual and reproductive education to mitigate the occurrence of sexual dysfunction, unplanned pregnancies, or sexually transmitted infections. Also, research addresses public health issues related to the prevention and/or intervention of sexual risk behaviors and sexual dysfunctions, highlighting their significance in sexual education and clinical practice.(AU)

Preservación de la función eréctil tras la uretroplastia: ¿escisión y anastomosis primaria o injerto de mucosa oral? / The best method for erection function in urethroplasty; is excision and primary anastomosis or buccal mucosal graft urethroplasty?

Introducción El objetivo de este estudio es evaluar y comparar la función eréctil (FE) tras la uretroplastia por escisión y anastomosis primaria (UEAP) y la uretroplastia con injerto de mucosa oral (UIMO) en la estenosis de uretra bulbar. Métodos Se identificó retrospectivamente a los pacientes tratados mediante uretroplastia. Se determinaron como criterios de inclusión en el estudio la edad entre 18 y 70 años y ser sexualmente activo. Los criterios de exclusión fueron la disfunción eréctil grave preoperatoria, estenosis distinta de la uretra bulbar, incompatibilidad psicosocial, estenosis uretral relacionada con fractura pélvica y tiempo de seguimiento inferior a un año. Como criterio de valoración primario, se utilizó el International Index of Erectile Function-5 (IIEF-5) para la comparación de la FE en el preoperatorio y en el 3.°, 6.° y 12.° mes tras la intervención quirúrgica. El criterio de valoración secundario fue el efecto de los datos demográficos, las características de la estenosis y del tratamiento sobre la FE. Resultados Tras aplicar los criterios de inclusión y exclusión, se identificó a 50 pacientes. De ellos, 30 fueron tratados mediante UEAP y 20 mediante UIMO. Al 3.er mes de la intervención, la FE mostró una disminución estadísticamente significativa en el grupo UEAP. En ambos grupos de pacientes se observó una mejoría de los efectos negativos postoperatorios sobre la EF en el 6.° mes, que recuperaron su nivel basal a los 12 meses. Conclusión Las técnicas UEAP y UIMO tienen un efecto similar sobre la FE a medio y largo plazo y ambas pueden utilizarse con seguridad y eficacia en el grupo de pacientes adecuado. (AU)

Introduction The aim of this study is to evaluate and compare erection function (EF) after excision and primary anastomosis urethroplasty (EPAU) and buccal mucosal graft urethroplasty (BMGU) in bulbar urethral stricture. Methods Patients who underwent urethroplasty were identified retrospectively. The criteria for inclusion in the study were determined as being over 18 years old and under 70 years old, being sexually active. Exclusion criteria are: preoperative severe erectile dysfunction, stricture outside the bulbar urethra, psychosocial incompatibility, urethral stricture related to pelvic fracture, follow-up time less than a year. As the primary endpoint, the International Index of Erectile Function-5 (IIEF-5) was determined as a comparison of EF in the preoperative and 3rd, 6th and 12th months after surgery. The secondary endpoint was the evaluation of the effects of demographic data, stricture and treatment characteristics on EF. Results Fifty patients were identified considering the inclusion/exclusion criteria. It was observed that there were 30 patients who underwent EPAU and 20 patients who underwent BMGU. At the third month after surgery, EF showed a statistically significant decrease in the EPAU group. In both patient groups, it was observed that the early negative effects after the operation in EF started to improve in the 6th month and returned to the baseline level by the first year. Conclusion EPAU and BMGU techniques have a similar effect on EF in the medium and long term. Both methods can be used safely and effectively in the appropriate patient group. (AU)

Erección prolongada dolorosa / Prolonged painful erection

El priapismo es una erección peneana prolongada y dolorosa, que ocurre sin estímulo sexual previo. Existen dos tipos principales, el priapismo de alto flujo y el priapismo de bajo flujo. Aunque en la mayoría de las ocasiones la causa subyacente será desconocida, puede ser la primera manifestación de una enfermedad grave. En el paciente pediátrico con una erección prolongada se debe diferenciar entre la erección peneana recurrente y los distintos tipos de priapismo, puesto que cada entidad requiere un manejo concreto e implica un pronóstico diferente. (AU)

Priapism is a prolonged and painful penile erection, which occurs without prior sexual stimulation. There are two main types, high-flow priapism and low-flow priapism. Although on most occasions the underlying cause will be unknown, it may be the first manifestation of serious disease. In the pediatric patient with prolonged erection we must differentiate between recurrent penile erection and the different types of priapism since each entity requires a specific management and implies a different prognosis. (AU)

The usefulness of shear wave elastography in evaluating erectile dysfunction severity before and after prostaglandin E1 test.

Prostaglandin E1 intracavernous injection test is an established method for diagnosing erectile dysfunction. However, the evaluation is non-objective and often influenced by the evaluator's subjectivity. Herein, we measured and objectively evaluated shear wave elastography results of the corpus cavernosum before and after injection in 16 patients who underwent prostaglandin E1 testing. The response score of prostaglandin E1 tests were "1" in 2 cases, "2" in 2 cases, and "3" in 12 cases. The average transmission velocity before the injection and at the time of maximum erection after the injection were 2.21 m/s and 1.57 m/s, respectively. Transmission velocity decreased during erection in 14 of 16 cases (87.5%). The overall rate of change in transmission velocity due to injection was -26.7% and was significantly different between the poor (responses 1 and 2: -16.1%) and good erection (response 3: -30.2%) groups. To the best of our knowledge, this is the first attempt to evaluate erectile phenomenon using percutaneous ultrasonic elastography in Japan. Rate of change in shear wave transmission velocity due to prostaglandin E1 injection in the corpus cavernosum penis was associated with the degree of erection. Therefore, the rate of change in shear wave transmission velocity in the corpus cavernosum penis could be used as an objective index of erectile phenomenon. Percutaneous ultrasonic elastography is a non-invasive and useful test method for diagnosing erectile dysfunction, determining the therapeutic effect, and predicting prognosis.

Cldn4 overexpression promotes penile cavernous smooth muscle cell fibrotic response via the JNK signaling pathway.

BACKGROUND: Erectile dysfunction (ED), defined as the inability to achieve or maintain a penile erection sufficient to satisfy sexual behavior, is prevalent worldwide. AIM: Using previous research, bioinformatics, and experimental confirmation, we aimed to discover genes that contribute to ED through regulating hypoxia in corpus cavernosum smooth muscle cells (CCSMCs). METHODS: We used the Gene Expression Omnibus to acquire the sequencing data of the corpus cavernosum transcriptome for diabetic ED and nerve injury type ED rats. We intersected the common differentially expressed genes. Further verification was performed using single cell sequencing. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate whether the differentially expressed genes are found in the corpus cavernosum. We used induced hypoxia to assess cell viability changes, and we developed a lentivirus overexpressing Cldn4 for in vitro and in vivo experiments to measure changes in JNK signaling, fibrosis, hypoxia, and erectile function. OUTCOMES: Our results indicate that targeting the JNK pathway and decreasing local hypoxia may be better options for therapeutic intervention to improve erectile function. RESULTS: We identified Cldn4 and found its expression increased in the corpora cavernosa of the 2 datasets. In addition, we found that hypoxia can increase the expression of Cldn4, activate the JNK signaling pathway, and exacerbate fibrosis in CCSMCs. Cldn4 overexpression in CCSMCs activated the JNK signaling pathway and increased fibrotic protein expression. Last, rat corpus cavernosum overexpressing Cldn4 activated the JNK signaling pathway, increased local fibrosis, and impaired erectile function. CLINICAL IMPLICATIONS: Through bioinformatics and in vitro and in vivo experiments, we found that Cldn4 has a negative effect on ED, and targeting Cldn4 may provide new ideas for ED treatment. STRENGTHS AND LIMITATIONS: Although we have identified Cldn4 as a potential target for ED treatment, we have only conducted preliminary validation on CCMSCs, and we still need to further validate in other cell lines. CONCLUSION: CCSMC hypoxia leads to increased Cldn4, in both nerve injury and diabetic ED rat models, and promotes fibrosis by activating the JNK signaling pathway.

PKC Inhibition Improves Human Penile Vascular Function and the NO/cGMP Pathway in Diabetic Erectile Dysfunction: The Role of NADPH Oxidase.

Erectile dysfunction (ED) is a frequent and difficult-to-treat condition in diabetic men. Protein kinase C (PKC) is involved in diabetes-related vascular and cavernosal alterations. We aimed to evaluate the role of PKC in endothelial dysfunction and NO/cGMP impairment associated with diabetic ED in the human corpus cavernosum (CC) and penile resistance arteries (PRAs) and the potential mechanisms involved. Functional responses were determined in the CC and PRAs in patients with non-diabetic ED and diabetic ED undergoing penile prosthesis insertion. PKC activator 12,13-phorbol-dibutyrate (PDBu) impaired endothelial relaxations and cGMP generation in response to acetylcholine in the CC from non-diabetic ED. PDBu also impaired responses to a PDE5 inhibitor, sildenafil, in non-diabetic ED patients. Conversely, a PKC inhibitor, GF109203X, improved endothelial, neurogenic, and PDE5-inhibitor-induced relaxations and cGMP generation only in the CC in diabetic ED patients. Endothelial and PDE5-inhibitor-induced vasodilations of PRAs were potentiated only in diabetes. Improvements in endothelial function in diabetes were also achieved with a specific inhibitor of the PKCß2 isoform or an NADPH-oxidase inhibitor, apocynin, which prevented PDBu-induced impairment in non-diabetic patients. PKC inhibition counteracted NO/cGMP impairment and endothelial dysfunction in diabetes-related ED, potentially improving response to PDE5 inhibition.