Cavernosal Pressure Research Articles

The Role of Testosterone in Amplifying the Effect of a Phosphodiesterase Type 5 Inhibitor After Pelvic Irradiation

BackgroundAfter radiotherapy, the risk of hypogonadism increases, and the incidence of erectile dysfunction increases with time. AimWe investigated the effect of testosterone and a phosphodiesterase type 5 inhibitor (PDE5I) on erectile tissue after radiotherapy. Methods12 male Wistar rats were assigned to each of 5 groups (group C: control; group R: radiation; group RPT: radiation, testosterone, and a PDE5I; group RP: radiation and a PDE5I; and group RT: radiation and testosterone). A 12.5 Gy/fraction dose was administered to the rectum in groups R, RPT, RP, and RT. Udenafil (20 mg/kg) was administered daily via nasogastric tubes in group RPT and group RP for 4 weeks starting 1 day after radiotherapy. Testosterone enanthate (25 mg/kg, IM) was administered immediately after radiotherapy in group RT and group RPT. 6 rats from each group were used to evaluate endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and NOX2, and cavernosal pressure was evaluated in the other 6 rats in each group. OutcomeTestosterone enhanced the effect of PDE5I on penile tissue after radiotherapy by amplifying the nitric oxide synthase activity. ResultseNOS mRNA expression increased in response to either testosterone replacement or PDE5I administration after radiotherapy. nNOS mRNA expression did not significantly increase in response to testosterone replacement, but testosterone significantly enhanced the effect of PDE5I on nNOS mRNA expression. Testosterone significantly amplified the effect of PDE5I on both eNOS and nNOS protein expression. Both testosterone and PDE5I reduced NOX2 protein expression. The intracavernosal pressure during electrical stimulation showed that testosterone alone did not significantly enhance erectile function. Clinical TranslationClinicians should consider both hypoxic tissue damage and hypogonadism during and after radiation, and the combination of testosterone and PDE5I could be more beneficial for preserving erectile tissue than either individual treatment. Strengths & LimitationsThis study describes the role of testosterone in amplifying the effect of a PDE5I on pelvic radiotherapy-induced hypogonadism. However, we did not show the time-dependent effects of testosterone and PDE5I. ConclusionsDespite the fact that the intracavernosal pressure during electrical stimulation did not significantly increase with testosterone replacement after radiotherapy, important changes in nitric oxide synthase activity and superoxide regulation might have amplifying effects on erectile tissue. Therefore, we recommend that physicians monitor testosterone levels and should not hesitate to combine testosterone and PDE5I in cases of radiation-induced hypogonadism if testosterone replacement is not contraindicated.Lee DS, Sohn DW. The Role of Testosterone in Amplifying the Effect of a Phosphodiesterase Type 5 Inhibitor After Pelvic Irradiation. J Sex Med 2020;17:1268–1279.

Evaluation of effectiveness of antiandrogen treatments on cavernosal tissues in rats.

In this study, we aimed to compare changes in cavernosal tissues in rats with antiandrogen treatment and orchiectomy. A total of 42 Wistar albino rats were divided into four groups. Group I, control group,Group II, LH-RH was given for 1month, Group III-LH-RH+Bicalutamide was given for 1month, and Group IV was defined as orchiectomy and followed up for 1month. Measurements of intracavernosal pressure with different electrical stimuli and pathological findings of smooth muscle collagen in cavernosal tissues were examined. While the cavernosal pressure response in all the different electrical stimuli given in the control group and in all other groups was significantly lower than that in the other groups, it was statistically significant at 7.5 and 10V (p=.005, p<0001). According to the pathologic evaluation, the density of tissue collagen increased significantly in the other groups according to the control group. In groups 3 and 4, the density of 4+ collagen was found to be increased according to Groups 1 and 2. In the LH-RH alone group, it appears that there are no 4+ colloid density and less damage. According to these findings, the negative effect of LH-RH treatment on cavernosal tissues appears to be less.

Nerves in the Areas Posterior to the Prostate Base Contribute to Erectile Function: An Intraoperative Electrical Stimulation Assessment

To confirm the distribution of functional nerves involved in erectile function at the posterior of the prostate base, intraoperative nerve stimulation was performed during robot-assisted radical prostatectomy (RARP) METHODS: Several points at the posterior of the prostate and the posterolateral typical neurovascular bundle (NVB) were electrically stimulated at the level of the prostate base during RARP in patients with clinically localized prostate cancer. The prostate pedicle (PP), medial side of the PP (MPP), Denonvilliers' fascia (DF), and typical NVB were stimulated using bipolar electrodes. The changes in pressure at the middle of the urethra were measured using an inserted balloon-catheter to detect the increase in cavernosal pressure. Although the study included only 12 patients, each stimulation of the PP, MPP, and NVB induced evident urethral pressure responses in all patients. The median amplitude of the pressure responses was 5.49 (IQR 3.11-8.42), 6.00 (IQR 3.70-8.30), and 3.22 (IQR 2.48-7.19) cm H2O at the PP, MPP, and NVB, respectively. The amplitude of responses at the PP and MPP was not small compared with the responses at the typical NVB. Stimulations at the DF induced unstable weak urethral response alone or no response in all patients. We showed that electrostimulation of the PP and MPP increases the cavernosal pressure similar to the typical NVB stimulation. These findings indicate that maximal preservation of the tissues at the posterior area of the prostate base can contribute to optimal recovery of postoperative erectile function after nerve-sparing RARP.

Anatomic and Functional Outcome Following Distal Shunt and Tunneling for Treatment İschemic Priapism: A Single-Center Experience

BackgroundIschemic priapism (IP) is a urologic emergency that requires early intervention. The main aim of IP treatment is to relieve the cavernosal pressure and provide erectile function. AimThe aim of this study was to determine the correlation between preoperative risk factors (patient’s age, duration of priapism, preoperative erectile function) and postoperative erectile dysfunction (ED). MethodsThis retrospective study consisted of 25 patients diagnosed with refractory IP between 2009–2017. The diagnosis of IP was confirmed by medical history, physical examination, and cavernosal blood gas analysis. All of the patients underwent the T-shunt procedure ± tunneling after a failed initial intervention. ResultsThe mean age at the time of the IP diagnosis was 46.84 years (range 23–77). The average follow-up time of the study population was 40.4 months (range 3–114), and the median time from the occurrence of IP to surgery was 58 hours (range 24–240). In all cases, rapid resolution of the erection was achieved with the T-shunt ± tunneling procedure. In 1 patient, priapism recurred after 12 hours. Postoperative ED was reported by 16 (84.21%) patients, with degrees of mild, mild to moderate, and severe in 6, 1, and 9 of these cases, respectively. During the follow-up, the mean International Index of Erectile Function–5 (IIEF-5) score was 12.68 (range 5–23). Only 3 (15.78%) patients achieved successful sexual intercourse without any treatment. 6 (31.5%) patients required the aid of phosphodiesterase type 5 inhibitors, and 1 (5.26%) patient required the aid of a vacuum erection device. The 9 (47.36%) patients with severe ED failed to respond to medical treatment and were considered candidates for a penile implant. According to Kendall’s tau-b correlation coefficient analysis, there was a positive correlation between the preoperative and postoperative IIEF-5 scores (P = .005), whereas the patient’s age and duration of priapism were negatively correlated with the postoperative IIEF-5 score (P = .016 and P = .046, respectively). Clinical ImplicationsTreatment options of IP should be discussed with patients in terms of both preoperative erectile function and the duration of priapism. Strengths & LimitationsThe small sample size and retrospective nature of this study were the main limitations. ConclusionsDespite high success and low complication rates of T-shunt surgery, the rate of undisturbed erectile function is only 14.6%. The patient’s age, the existence of preoperative ED, and the duration of priapism are associated with postoperative IIEF-5 scores.Ortaç M, Çevik G, Akdere H, et al. Anatomic and Functional Outcome Following Distal Shunt and Tunneling for Treatment İschemic Priapism: A Single-Center Experience. J Sex Med 2019;16:1290–1296.

Decrease of the insulin-like growth factor-1 bioavailability in spontaneously hypertensive rats with erectile dysfunction.

We investigated the role of insulin-like growth factor-1 (IGF-1) in spontaneously hypertensive rats with erectile dysfunction. Firstly, we evaluated intracavernous pressure. The bioavailability of IGF-1 at both mRNA and protein levels were measured by quantitative real-time PCR and Western blot respectively. Then, cavernous cyclic guanosine monophosphate concentrations were detected by enzyme-linked immunosorbent assay. The cavernosal pressure was significantly decreased in the hypertensive and the propranolol treatment groups compared to the normal control group (P<0.01). Cavernous IGF-1 bioavailability and the concentrations of cavernous cyclic guanosine monophosphate were both significantly decreased in the hypertensive and the propranolol treatment groups compared to the normal control group (P<0.01). This study suggests that an obvious decrease in cavernous IGF-1 levels might play an important role in spontaneously hypertensive rats with erectile dysfunction.

Short hairpin ribonucleic acid constructs targeting insulin-like growth factor binding protein-3 rehabilitated dyslipidaemia in diabetic rats.

It was investigated whether short hairpin ribonucleic acid constructs targeting insulin-like growth factor binding protein-3 (IGFBP-3 shRNA) can rehabilitate dyslipidaemia in streptozotocin-induced diabetic rats. After 12 weeks of intracavernous administration of IGFBP-3 shRNA, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The concentrations of serum low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride and cavernous cyclic guanosine monophosphate were all detected by enzyme-linked immunosorbent assay. The per cent of smooth muscle in corpus cavernous tissue was also evaluated. It was found that the cavernosal pressure was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic control group after 12 weeks of intracavernous administration of IGFBP-3 shRNA (P < 0.01). The concentrations of serum low-density lipoprotein cholesterol and triglyceride were significantly decreased in the IGFBP-3 shRNA treatment group compared to the diabetic control group, while no significant changes of serum high-density lipoprotein cholesterol concentration were found (P < 0.01). At the same time, cavernous cyclic guanosine monophosphate concentrations and the percentage of cavernosal smooth muscle were both significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic control group (P < 0.01). This study indicated that IGFBP-3 shRNA might rehabilitate erectile function via a decrease in concentrations of serum low-density lipoprotein and triglyceride, an increase in the percentage of cavernosal smooth muscle and an improvement in the nitric oxide-cyclic guanosine monophosphate signalling activities in streptozotocin-induced diabetic rats.

Short hairpin ribonucleic acid constructs targeting insulin-like growth factor binding protein-3 rehabilitated decreased testosterone concentrations in diabetic rats.

BackgroundThe aim of this study was to determine if shRNA constructs targeting insulin-like growth factor binding protein-3 can rehabilitate decreased serum testosterone concentrations in streptozotocin-induced diabetic rats.Material/MethodsAfter 12 weeks of intracavernous administration of IGFBP-3 shRNA, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The expression of IGFBP-3 at mRNA and protein levels was detected by quantitative real-time PCR analysis and Western blot, respectively. The concentrations of serum testosterone and cavernous cyclic guanosine monophosphate were detected by enzyme-linked immunosorbent assay.ResultsAfter 12 weeks of intracavernous administration of IGFBP-3 shRNA, the cavernosal pressure was significantly increased in response to the cavernous nerves stimulation compared to the diabetic control group (p<0.01). Cavernous IGFBP-3 expression at both mRNA and protein levels was significantly inhibited. Both serum testosterone and cavernous cyclic guanosine monophosphate concentrations were significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic control group (p<0.01).ConclusionsThese results suggest that IGFBP-3 shRNA may rehabilitate erectile function via increases of concentrations of serum testosterone and cavernous cyclic guanosine monophosphate in streptozotocin-induced diabetic rats.

Increased expression of insulin-like growth factor-binding protein-3 is implicated in erectile dysfunction in two-kidney one-clip hypertensive rats after propranolol treatment

This study aimed to investigate the role of insulin-like growth factor-binding protein-3 (IGFBP-3) in erectile dysfunction (ED) in two-kidney one-clip (2K-1C) hypertensive rats treated with the β-blocking agent propranolol. Adult male Wistar rats were randomly divided into three groups: a normal control group, a hypertensive control group and a propranolol treatment group (n=9). After 4 weeks of propranolol treatment, intracavernous pressure (ICP) responses to electrical stimulation of the cavernous nerves were evaluated. The expression of IGFBP-3 and insulin-like growth factor-1 (IGF-1) mRNA and protein in the rat cavernous tissue were detected by quantitative real-time PCR and Western blot, respectively. The concentration of cyclic guanosine monophosphate (cGMP) in the cavernous tissue was determined by enzyme-linked immunosorbent assay (ELISA). Cavernosal pressure in response to cavernous nerve stimulation was decreased 4 weeks after propranolol treatment (P<0.01, compared to the hypertensive control group). IGFBP-3 mRNA and protein expression was increased in the propranolol treatment group compared to the hypertensive control group (P<0.01), whereas IGF-1 expression was decreased in the propranolol treatment group compared to the hypertensive control group (P<0.01). In addition, cavernous cGMP concentration was decreased in the propranolol treatment group compared to the hypertensive control group (P<0.01). Taken together, these results suggest that the upregulation of IGFBP-3 may play a role in the development of ED in hypertensive rats.

753 A COMPARISON OF INTRACAVERNOSAL AND INTRASPONGIOSAL PRESSURE RECORDING USING THE TELEMETRIC DEVICE IN CONSCIOUS RATS

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research1 Apr 2011753 A COMPARISON OF INTRACAVERNOSAL AND INTRASPONGIOSAL PRESSURE RECORDING USING THE TELEMETRIC DEVICE IN CONSCIOUS RATS Jun-Ho Lee, Sung Won Lee, Mikyeong Ko, Mee Ree Chae, Hyunjung Kim, Deok Hyun Han, Woo Jung Kim, Sung Chul Kam, Jong Kwan Park, Ju-Hong Jeon, and Insuk So Jun-Ho LeeJun-Ho Lee Seoul, Korea, Republic of More articles by this author , Sung Won LeeSung Won Lee Seoul, Korea, Republic of More articles by this author , Mikyeong KoMikyeong Ko Seoul, Korea, Republic of More articles by this author , Mee Ree ChaeMee Ree Chae Seoul, Korea, Republic of More articles by this author , Hyunjung KimHyunjung Kim Seoul, Korea, Republic of More articles by this author , Deok Hyun HanDeok Hyun Han Seoul, Korea, Republic of More articles by this author , Woo Jung KimWoo Jung Kim Seoul, Korea, Republic of More articles by this author , Sung Chul KamSung Chul Kam Jinju, Korea, Republic of More articles by this author , Jong Kwan ParkJong Kwan Park Jeonju, Korea, Republic of More articles by this author , Ju-Hong JeonJu-Hong Jeon Seoul, Korea, Republic of More articles by this author , and Insuk SoInsuk So Seoul, Korea, Republic of More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1778AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The current widely used method to quantify erectile function is intracavernosal pressure (ICP) assessment in anesthetized animals using cavernous nerve stimulation model which has obviously the drawbacks of the animal being unconscious and assessment being done in a single time point. Telemetric monitoring of ICP and intraspongiosal pressure (ISP) in freely moving rats was introduced to evaluate erectile function under physiological conditions. But there is no report about which one is more suitable for evaluating erection. In the present study, we compared ICP with ISP in normal rat (n=6). METHODS Adult rats (Sprague-Dawley; 18 weeks aged) were implanted in the corpus cavernosum and corpus spongiosum with a pressure sensor (model C40; Data Sciences, St. Paul, MN) which permitted telemetric monitoring of cavernosal pressure in freely moving animals following subcutaneous injection of a single dose of apomorphine (100μg/kg). First peak after injection(s), number of events, duration(s), maxinum ICP/ISP (ICPMax/ISPMax), area under the curve (AUC), sum area under the curve (sum AUC) recorded during apomorphine erection tests. Also, sexual events were visually identified and video recorded. RESULTS An erectile event was defined as an episode, which begins by a gradual increase in the cavernosal pressure and followed by multiple supeimposed very brief surges in the pressure, and ends by gradual decline of the pressure to reach baseline levels. As for the ICP recording, Number of penile erectile events for 30 min. was 2.2±0.3, and it corresponded to visually detected penile erections. Latency for the first penile erection event was 307.1±49.8 sec. Mean ICPMax, mean AUC, and mean sum AUC were 193.6±66.4 mmHg, 1401.4±301.3 mmHg·s, and 2895.7±827.2 mmHg·s, respectively. But, ISP recording showed no typical pressure change as shown in ICP recording. There were only 3.0±1.0 events that include simple 10 peaks without baseline pressure increase (>450mmHg*s), and it was less than 5 sec. And it was difficult to analysis because its artifact. CONCLUSIONS ICP recording by using telemetry device provided a consistent and accurate data during erectile events, while ISP recording was difficult to identify changes of intrapenile pressure due to its artifact. Further work is required to establish a standard analysis ISP recording method for more effective evaluation of erectile activity during telemetry recording. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e303 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jun-Ho Lee Seoul, Korea, Republic of More articles by this author Sung Won Lee Seoul, Korea, Republic of More articles by this author Mikyeong Ko Seoul, Korea, Republic of More articles by this author Mee Ree Chae Seoul, Korea, Republic of More articles by this author Hyunjung Kim Seoul, Korea, Republic of More articles by this author Deok Hyun Han Seoul, Korea, Republic of More articles by this author Woo Jung Kim Seoul, Korea, Republic of More articles by this author Sung Chul Kam Jinju, Korea, Republic of More articles by this author Jong Kwan Park Jeonju, Korea, Republic of More articles by this author Ju-Hong Jeon Seoul, Korea, Republic of More articles by this author Insuk So Seoul, Korea, Republic of More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Restraint Stress Impairs Erectile Responses in Rats

It has been established that various forms of physical and psychological stress reduce sexual functions. However, there is no study yet evaluating the functional changes over cavernosal pressure in rats exposed to restraint stress. In this study, we aimed to investigate the convenience of the restraint stress model that may be used to determine the disruptive effects of stress on erectile function. Sprague Dawley rats were randomized into two groups as control (n = 7) and stress (n = 7) groups. In the stress group, rats were placed for 60 minutes in a cylindrical plastic tube with holes for fresh air supply (restraint stress). Following the stress application, several parameters for erectile responses were evaluated immediately. The control animals were maintained at room temperature without any procedure until the measurement. During the electrical stimulation of cavernous nerve, we measured the intracavernous pressure (ICP), the ratio of ICP to the mean arterial pressure (MAP), and detumescence time. There were significant decreases in ICP (24.4 +/- 4.1 vs 53.4 +/- 4.5 mmHg, p < 0.01), ICP/MAP (34.4 +/- 7.8% vs 55.7 +/- 3.9%, p < 0.05), and detumescence time (31.7 +/- 6.1 vs 78.6 +/- 12.8 sec, p < 0.01) in stress group when compared to control group. Thus, restraint stress declined detumescence time and decreased intracavernosal pressure in male rats. In conclusion, restraint stress model in rats may be useful for determining the effects of stress on erectile response. Even a short-term restraint stress may cause erectile dysfunction.

Nerves at the Ventral Prostatic Capsule Contribute to Erectile Function: Initial Electrophysiological Assessment in Humans

BackgroundRecent microanatomical studies have identified a significant amount of nerve fibers along the ventral circumference of the prostate capsule and confirmed the concept of a periprostatic nerve network. However, functional investigations have not yet proved whether nerve fibers distributed on the prostate capsule, particularly those outside the neurovascular bundle (NVB), contribute to erection. ObjectiveTo confirm whether nerve fibers distributed on the prostate capsule contribute to erectile function, the present study was performed using electrophysiologic testing. Design, setting, and participantsThe circumference of the prostate capsule was electrically stimulated during radical retropubic prostatectomy (RRP) in 12 patients with clinically localized prostate cancer (PCa). We defined the ventromedian circumference of the prostate capsule as the 12 o’clock position and the posterolateral position of the typical NVB as the 5 o’clock position. Periprostatic nerve fibers at the 12, 1, 2, 3, 4, and 5 o’clock positions of the midprostate were stimulated using bipolar electrodes. MeasurementsChanges in pressure at the middle of the urethra were measured using an inserted balloon catheter to detect increases in cavernosal pressure. Results and limitationsAlthough the study included only 12 patients, every stimulation at all positions between 1 and 5 o’clock evoked urethral pressure responses in all patients. Mean pressure response was most powerful for 5 o’clock stimulation and decreased with stimulated points further from the 5 o’clock position. ConclusionsWe demonstrated that electrostimulation at not only the posterolateral but also the anterior and lateral circumference of the prostate capsule can increase cavernosal pressure. These findings indicate that the periprostatic nerve network contributes to erections.

Structural and functional investigations of the murine cavernosal nerve: a model system for serial spatio‐temporal study of autonomic neuropathy

To illustrate the ultrastructural fibre composition of the rat cavernosal nerve at serial levels, from its origin in the main pelvic ganglion to its termination in the corpus cavernosum of the distal penile shaft, and to develop a technique that permits repeated electrophysiological recording from the fibres that form the cavernosal nerve distinct from the axons of the dorsal nerve of the penis (DNP). For the light microscope and ultrastructural studies, Sprague-Dawley rats were anaesthetized and the pelvic organs and lower limbs were perfused with glutaraldehyde through the distal aorta. Tissue samples were embedded in epoxy resin and prepared for light and electron microscopy. Frozen tissue was used for the immunohistochemical studies and sections were stained with rabbit anti-nitric oxide synthetase 1 (NOS1). For the electrophysiology, anaesthetized rats were used in sterile conditions. Nerve conduction velocity for the cavernosal nerve was assessed from a point 2 mm below the main (major) pelvic ganglion after stimulating the nerve at the crus penis; multi-unit averaging techniques were used to enhance the recording of slow-conduction activity. Recordings from the DNP were obtained over the proximal shaft after stimulation at the base of the penis. Step-serial sections of the cavernosal nerve revealed numerous ganglion cells in the initial segments and gradually fewer myelinated fibres at distal levels. At the point of crural entry, the nerve contained almost exclusively unmyelinated axons. As it descended the penile shaft, the nerve separated into small fascicles containing only one to four axons at the level of the distal shaft. In the corpus cavernosum, vesicle-filled presynaptic axon preterminals were close to smooth muscle fibres, but did not seem to be in direct contact. Immunohistochemical evaluation of NOS1 activity showed intense staining of the fibres of the DNP and most of the neurones in the main pelvic ganglion. There was also scattered NOS1 activity in the nerve bundles of the corpus cavernosum. Electrophysiology identified activity in C fibres on the cavernosal nerve and in Aalpha-Adelta fibres in the DNP. These results show that it is possible to perform integrated cavernosal pressure monitoring and ultrastructural and electrophysiological studies in this model. These yielded accurate data about the erectile status of the penis, and the state of unmyelinated and myelinated fibres in the DNP and cavernosal nerves of the same animal. This study provides a useful template for future studies of experimental diabetic autonomic neuropathy.

Cavernosus Muscle Contraction During Erection: Is It Voluntary or Reflex, Given the Striated Nature of the Muscles?

The bulbo- and ischio-cavernosus muscles (BCM, ICM) contract in the rigid erection phase, leading to a suprasystolic cavernosal pressure. We investigated the hypothesis that the contraction of cavernosal muscles is reflexogenic despite their striated nature. The intracavernosal pressure (ICP) and the cavernosus muscles' electromyography (EMG) were recorded in 18 healthy volunteers in the flaccid and erectile phases. The test was repeated after separate anesthetization of the cavernosus muscles and the corpora cavernosa while the penis was in the rigid erection phase. The ICM and BCM showed no EMG activity with tumescence and full erection. When the ICP reached a mean of 148.6 +/- 9.4 cm H2O, both the ICM and BCM showed increased EMG activity. The suprasystolic pressure was intermittent and corresponded to the intermittent BCM and ICM contraction. Voluntary cavernosus muscle contraction did not increase the ICP at the different stages of erection. Anesthetization of the penis in the rigid erection phase led to disappearance of the cavernosus muscles' EMG activity, while bland gel application did not. Anesthetization of the 2 contracting cavernosus muscles, while the penis was in the rigid phase, produced an ICP drop to 69.5 +/- 7.6 cm H2O; repetition with saline did not affect the ICP. Cavernosus muscle contraction on corporal pressure elevation seems to be reflex and mediated through the corporo-cavernosal reflex (CCR). Changes in the evoked response amplitude would indicate a defect in the reflex pathway.

Improvement in erectile dysfunction after insulin-like growth factor-1 gene therapy in diabetic rats

To determine whether adenoviral gene transfer of insulin like growth factor-1 (IGF-1) to the penis of streptozotocin (STZ)-induced diabetic rats could improve erectile capacity. THE STZ diabetic rats were transfected with AdCMV-betagal or AdCMV-IGF-1. These rats underwent cavernous nerve stimulation to assess erectile function and their responses were compared with those of age-matched control rats 1 to 2 days after transfection. In control and transfected STZ diabetic rats, IGF-1 expression were examined by reverse transcription polymerase chain reaction (RT-PCR), Western blot and histology. The penis beta-galactosidase activity and localization of the STZ diabetic rats were also determined. One to two days after transfection, the beta-galactosidase was found in the smooth muscle cells of the diabetic rat penis transfected with AdCMV-betagal. One to 2 days after administration of AdCMV-IGF-1, the cavernosal pressure, as determined by the ratio of maximal intracavernous pressure-to-mean arterial pressure (ICP/MAP) and total intracavernous pressure (ICP), was increased in response to cavernous nerve stimulation. Transgene expression was confirmed by RT-PCR, Western blot and histology. Gene transfer of IGF-1 significantly increased erectile function in the STZ diabetic rats. These results suggest that in vivo gene transfer of IGF-1 might be a new therapeutic intervention for the treatment of erectile dysfunction (ED) in the STZ diabetic rats.

Dysregulation of Dimethylarginine Dimethylaminohydrolase Causes Elevation of Asymmetric Dimethylarginine in a Rat Model of Vasculogenic Erectile Dysfunction

Purpose: Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) and the major metabolic pathway of ADMA is enzymatic degradation via dimethylarginine dimethylaminohydrolasease (DDAH). In this study, we hypothesized that an elevated cavernosal ADMA level might result from poor DDAH activity in the corpus cavernosum. We examined whether ADMA was accumulated in our atherosclerotic rat model of vasculogenic erectile dysfunction (VED). Materials and Methods: Twelve 12-wk-old Sprague-Dawley rats were grouped in either the atherosclerosis group (AS, n=6) or the control (n=6) group. The AS group received a 1% cholesterol diet for 6 weeks and the rats were also treated with NG-nitro-L-arginine methyl ester (3mg/ml) for the initial 2 weeks. The control group received a normal diet. Six weeks later, all the rats were anesthetized with urethane (1.6g/kg) and cavernous electrostimulation was done under continuous arterial and cavernosal pressure monitoring (6V, 0.5ms, 20Hz, 50sec). The methylarginine level in both the AS group and the control group was measured respectively. Also, the NOS activity and DDAH activity in the corpus cavernosum were evaluated. Results: Upon cavernous electostimulation, the peak intracavernosal pressure (ICP) of the control group was 88.5±5.5mmHg (n=6). In contrast, the peak ICP level was markedly reduced in the atherosclerotic group to 54.2±4.8mmHg (n=6, p<0.001). The cavernosal level of ADMA in the control group was 320.5±23.6μM and it was 860.7±34.7μM in the AS group. The constitutive NOS activity in the rat corpus cavernosum of the AS group was markedly reduced compared to the control group. Also, the cavernosal DDAH activity was reduced in the AS rats and the activity showed significant negative correlation with the cavernosal ADMA level. Conclusions: In this study, we have demonstrated that the dysregulation of DDAH activity may be one of the causes of decreased NOS activity in atherosclerotic erectile dysfunction. (Korean J Urol 2006;47:1079-1085)

Cavernosal nerve mapping: current data and applications.

Although nerve-sparing prostatectomy is widely practised, the results with respect to preserving potency often do not meet expectations. The concept of intraoperative cavernosal nerve stimulation is reasonable. Data that link the response to sildenafil after prostatectomy with bilateral nerve sparing has increased the importance of optimizing nerve sparing. The cavernosal nerves are often difficult to visualize and may have a variable course. A tumescent response to nerve stimulation can be shown consistently; the response may be subtle, and characterized by a minimal increase in penile circumference and blood flow. Immediately after prostatectomy, proximal nerve stimulation identifies whether neural continuity has been maintained, and is predictive of recovery of erectile function. The Cavermap system (Uromed Corporation, Boston, MA, USA) was developed to permit intraoperative nerve stimulation with tumescence monitoring. An initial phase 2 and subsequent phase 3 single-blinded, randomized, multicentre study that compared Cavermap-assisted prostatectomy with conventional nerve sparing showed a significant benefit in terms of the duration of nocturnal tumescence at 1 year. Other approaches are being explored, including incorporating the device into sural or genito-femoral nerve grafting, use of nerve stimulation during cystectomy or abdominal-perineal resection, and direct corpus cavernosal pressure monitoring during nerve stimulation. These approaches warrant further evaluation.

Improved erectile function after Rho-kinase inhibition in a rat castrate model of erectile dysfunction.

Androgens are reported to act as strong modulators of erectile function influencing both nitric oxide and vasoconstrictor signaling. Castration results in a depressed erectile response that is associated with a loss of nitric oxide production and increased responsiveness to constrictive agents. The increased vasoconstrictor response may be a result of an active RhoA/Rho-kinase signaling pathway. We report here results of studies designed to test the hypothesis that inhibition of the Rho-kinase pathway restores erectile function in a castrate model by relaxing the smooth muscle. Mean arterial (MAP) and corpus cavernosal (CCP) pressures were monitored during intracavernosal injection of the Rho-kinase inhibitor Y-27632. Castration reduced the maximal erectile response (CCP/MAP) by 33%, and testosterone replacement restored the response (intact, 0.736 +/- 0.040; castrate, 0.492 +/- 0.022; testosterone, 0.681 +/- 0.073). Injection of Y-27632 increased CCP in all experimental groups; it also left shifted the voltage response curve and increased the maximal CCP/MAP response (intact, 0.753 +/- 0.091; castrate, 0.782 +/- 0.081; testosterone treated, 0.894 +/- 0.033). Y-27632 dose dependently relaxed phenylephrine-stimulated cavernosal tissues. Cavernosal tissues showed increased RhoA and Rho-kinase protein levels after castration. Our data support the hypothesis that an active Rho/Rho-kinase pathway contributes to the reduced erectile response after castration due to an upregulation of RhoA/Rho-kinase protein levels and that inhibition of this pathway may serve as an effective treatment for erectile dysfunction.

Activation of central melanocortin receptors by MT-II increases cavernosal pressure in rabbits by the neuronal release of NO.

1. Melanotan-II had been reported to cause penile erections in men with erectile dysfunction. In the present study, we investigated the mechanisms by which systemic administration of MT-II increases intracavernosal pressure in anaesthetized rabbits. 2. MT-II (10 microM) had no effect on electrical field stimulation-evoked relaxations of rabbit corpus cavernosal strips in vitro. 3. Intravenous injection of MT-II (66 and 133 microg kg(-1) elicited dose-related increases in cavernosal pressure. SHU 9119 (3 microg kg(-1), i.v.), a non-selective antagonist of MC(3) and MC(4) receptors did not significantly affect either cavernosal pressure or systemic blood pressure but abolished the MT-II-induced increases in cavernosal pressure. SHU 9119 also inhibited the depressor response produced by MT-II. 4. Intracavernosal injection 100 microl of the cocktail containing phentolamine mesylate (1 mg ml(-1)), papaverine (20 mg ml(-1)) and PGE1 (20 microg ml(-1)) increased the cavernosal pressure by about 4 fold. 5. The role of NO-cyclic GMP dependent pathway to MT-II-induced increases in cavernosal pressure was investigated by bilateral transection of the pudendal nerves and by inhibition of NO synthase with L-NAME (20 mg kg(-1), i.v. over 30 min). Ablation of the pudendal nerves or pretreatment with L-NAME abolished the MT-II-induced increases in intracavernosal pressure in anaesthetized rabbits. 6. The data suggest that activation of central melanocortin receptors by MT-II increases cavernosal pressure by the neuronal release of NO.

Injured external anal sphincter in erectile dysfunction.

The purpose of this study was to investigate the function of the bulbocavernosus muscle in patients with faecal incontinence as a result of injury to the external anal sphincter, and to find out whether faecal incontinence had any role in erectile dysfunction. The study comprised 16 men (age 41.6+/-6.8 years) whose erectile dysfunction and faecal incontinence followed an operation for anal fistula. Erection could not be maintained until ejaculation, which, if it did occur, was not in jets. Ten healthy volunteers acted as controls. The activity of the external anal sphincter and the bulbocavernosus muscle was recorded by electromyography; anal and penile bulb pressures were also recorded. Investigations showed that erectile function was normal. The external anal sphincter was repaired, and faecal control and erectile dysfunction were assessed. Patients were followed up for 19.6+/-3.2 months. The results showed that the bulbocavernosus reflex elicited no response in either the sphincter or the bulbocavernosus muscle. Their activity, recorded by electromyography, as well as anal and bulbar pressures at rest and on voluntary squeeze, and electrostimulation of the external anal sphincter, showed a significant reduction compared to the controls. Sphincteroplasty made the patients continent and restored erectile function and ejaculation to normal. We conclude from the current study that the reduced activity of the bulbocavernosus muscle is probably caused by injury to the external anal sphincter. It is suggested that erectile dysfunction is caused by the failure, during erection, of the contraction of the bulbocavernosus muscle to raise cavernosal pressure above systolic blood pressure. The loss of the rhythmical contractions of the bulbocavernosus muscle is probably why ejaculation did not occur in jets. Repair of the external anal sphincter provided a cure for faecal incontinence and erectile dysfunction. Anorectal disorders are believed to affect erectile function, a relationship that needs further investigation.

Nitric Oxide-Mediated Erectile Effects of Galantide but Not Galanin in Vivo

The purpose of this study was to investigate the in vivo effects of intracavernosal injections of galanin and galantide (a specific galanin receptor antagonist) on penile erection in the anesthetized cat. Erectile responses to galanin and galantide were compared with responses to a standard triple drug combination [1.65 mg papaverine, 25 μg phentolamine, and 0.5 μg prostaglandin E1 (PGE1)]. Intracavernosal injections of galanin (3–100 nmol) and galantide (0.1–3 nmol) induced penile erection in a dose-dependent manner. In terms of relative potency, galantide was approximately 100-fold more potent than galanin at increasing cavernosal pressure. The maximal increases in intracavernosal pressure in response to galanin and galantide were 83 and 95%, respectively, of the control triple drug combination. The total durations of erectile response caused by these peptides were significantly shorter (P < 0.05) than those by the triple drug combination. The nitric oxide synthase inhibitor L-NAME (20 mg) significantly decreased the erectile response in the cat to galantide but not to galanin, while the K+ATP channel antagonist U-37883A (3 mg) had no effect on the erectile response to galanin nor galantide. The results of the present study demonstrate that galantide, a putative antagonist for the galanin receptor, has more potent agonist activity than galanin in increasing intracavernosal pressure in the cat. Moreover, these data suggest that galantide, but not galanin, causes penile erection by an NO/cGMP-dependent mechanism. This is the first study to demonstrate that galanin may play a role in the physiology of penile erection.