Effects of castration and testosterone replacement on veno-occlusion during penile erection in the rat

Aim: To determine if androgens directly regulate veno-occlusion or if androgens act indirectly to maintain the penilestructures which control outflow. Methods: Using CASTRATE and TESTO rats, measurement was made of meanarterial pressure (MAP), intracavernosal pressure (CCP), and intracavernosal flow (CCF) during erection resultingfrom stimulation of the autonomic innervation of the penis. CCP and CCF were also measured during saline infusioninto the cavernosal sinuses before and after treatment with sodium nitroprusside (SNP, a nitric oxide donor drag) tofully relax cavernosal smooth muscle. Penile tissue was also collected to measure the content of α actin and proline andhydroxyproline to determine if brief withdrawal of androgenic support led to changes in the number of smooth musclecells or the collagen content of the tissue. Results: Infusion of saline into the cavernosal sinuses demonstrated thatveno-occlusion was defective in CASTRATE rats while reno-occlusion was fully functional in TESTO animals.Furthermore, veno-occlusion could be induced in CASTRATE rats if they were first treated with SNP. Thisobservation suggests that failure of veno-occlusion in the CASTRATE rats is due to a deficiency in the production of NOresulting in a reduction in the degree of relaxation of the penile smooth muscle. The measurements of smooth muscleα actin and proline and hydroxyproline content of collagen showed that both were unaffected by castration and that thebasic structure of the penis did not degenerate after one week without androgenic support. Conclusion: Theseresults can be interpreted to mean that androgens control the veno-occlusive mechanism indirectly via a NO dependentmechanism and not by maintaining the structures of the penis which are essential to reno-occlusion.

Effect of sildenafil citrate on penile erection of rhesus macaques

Aim: To examine the effect of sildenafil citrate on penile erection of male rhesus macaque. Methods: Twenty Macaca mulatta were divided into the sildenafil treated and the control groups of 10 animals each. The penile size, the corpus cavernosal electromyogram (EMG) and the intra-corpus cavernosal pressure (ICP) were determined. Results: The diameter of penis and the ICP were significantly increased and the corpus cavernosal EMG significantly reduced in the sildenafil group. Conclusion: Sildenafil citrate increases the penile size and ICP and reduces the corpus cavernosal EMG in male rhesus macaque.

Potentiation of apomorphine effect on sildenafil-induced penile erection in conscious rabbits

Aim: To investigate a possible potentiation effect of apomorphine (APO) on sildenafil-induced penile erection in the conscious rabbit. Methods: Erection of male New Zealand White rabbits (3.5-4.0 kg, n=12) was assessed by measuring the length of the uncovered penile mucosa and the duration of erection before and after intravenous administration of agents. After injection of APO (0, 0.05, 0.1 and 0.4 mg/kg), sildenafil was administered intravenously in a dose-response manner (0.5, 1 and 5 mg/kg). In additional experiments, the effect of increasing doses of sildenafil in combination with APO on systemic blood pressure was evaluated. Results: Systemic administration of sildenafil induced a dose-dependent increase in the penile length. Intravenous injection of APO alone did not produce any change in the penile length, while significantly enhanced the penile erection induced by sildenafil. The co-administration of 0.1 mg/kg of APO and 1 mg/kg of sildenafil was found to be the most effective combination in producing penile erection. Intravenous administration of sildenafil caused a concentration-dependent decrease in systemic blood pressure, but no additional decrease was observed with co-administration of APO. Conclusion: APO enhances the penile erection induced by sildenafil in the conscious rabbit without causing an additional decrease in blood pressure.

Possible Function of Frenulum of Prepuce in Penile Erection

Objective To discuss the possible function of frenulum of prepuce in penile erection. Methods Nine patients had premature ejaculation whose frenula were short. Two patients suffered unsatisfied intercourse whose frenula were injured and departed 12 and 6 months ago. Three males endured premature ejaculation whose frenula were hurt in coition 30 min ago.We prolonged short frenulum and reconstructed the ruptured frenulum. To the fresh wound,we debrided the cut,then sutured the injured frenulum vertically. Results Investigated 3 to 6 months,all patients got satisfied sexual intercourse. Conclusion Frenulum is important in erecting time.

Beneficial Effect of Berberis amurensis Rupr. on Penile Erection

Objective： To investigate whether the methanol extract of Berberis amurensis Rupr. （BAR） augments penile erection using in vitro and in vivo experiments. Methods： The ex vivo study used corpus cavemosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure （ICP）, blood pressure, mean arterial pressure （MAP）, and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats. Results： Preconstricted with phenylephrine （PE） in isolated endothelium- intact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester （L-NAME）, a nitric oxide synthase inhibitor, and 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-l-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME 1H-[1,2,4]- oxadiazole-[4,3-α ]-quinoxalin-l-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium （TEA, P〈0.01）, a nonselective K＋ channel blocker, 4-aminopyridine （4-AP, P〈0.01）, a voltage-dependent K＋ channel blocker, and charybdotoxin （P〈0.01）, a large and intermediate conductance Ca2. sensitive-K＋ channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently. Conclusion： BAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca2. sensitive-K＋ （BK＋ and IK＋） channels in the corpus cavemosum.

The effects of androgen on penile reflex, erectile response to electrical stimulation and penile NOS activity in the rat

Aim: To investigate the effects of androgen on penile erection through the reflex arc and penile corpus cavernosum,and study the respective roles of testosterone (T) and dihydrotestosterone (DHT) in penile erection in rats. Methods:Male Sprague-Dawley rats were castrated and implanted with silastic brand silicone tube containing T or DHT, with orwithout daily injections of a 5α-reductase inhibitor, MK-434. The penile reflex, erectile response to electrical stimula-tion (ES) of the cavernous nerves and penile nitric-oxide synthase (NOS) activity were observed under varying andro-genic status. Results: Penile reflex erection in the rat was, on the whole, related to serum T levels though the numberof glans engorgements was not. The number of cups and flips was significantly decreased by castration, and restoredto the control level by T supplementation. Erectile response to ES and NOS activity in penile tissue was also related toserum T level. T administered together with a 5α-reductase inhibitor no longer restored the number of reflex erection,erectile responses to ES and NOS activity in the corpus cavernosum. Conclusion: Androgen influenced the penile re-flex arc, corpus cavernosum, and the perineal striated muscles. In reflex erection, erectile response to ES and penileNOS activity in the rat, T seems to be first converted to DHT, the more active androgen modality. (Asian J Androl1999 Dec; 1: 169-174)

Selective control by posterior spinal nerve roots of micturition and erection in rats

The posterior rootlets in L6 and S1 spinal cord of adult male Sprague-Dawley rats underwent electrostimulation. The bladder pressure, urethral perfusion pressure and intracavernous pressure were recorded. When some posterior rootlets of L6 and Sl were electrostimulated, the intracavernous pressure peaked rapidly, but the bladder pressure and the urethral perfusion pressure curve did not show great change. When other rootlets were stimulated, the bladder pressure changed greatly, but the urethral perfusion pressure and the intracavernous pressure did not show great change. When different rootlets were stimulated, the urethral perfusion pressure changed maximally, but there were no great changes in bladder pressure or intracavernous pressure. Furthermore, stimulation of some rootlets produced simultaneous changes in two or three different pressure measures mentioned above. The results demonstrate that regulation by L6 and S1 posterior rootlets of the rat bladder detrusor, external urethral sphincter and penis cavernous body are significantly distinct. Different rootlets can be distinguished by electrostimulation.

Role of the brain in the control of erection

In contrast to the spinal control of erection, relatively little is known about the brain control. In the present review, we have outlined the role of brain structures involved in penile erection and provided a synopsis on the brain circuit of erection. Findings from both animal and human studies are discussed. Evidence suggests that the most important structures are the frontal lobe, cingulate gyrus, amygdala, thalamus and hypothalamus. Within the brain circuit of erection, the thalamus serves as a gate-controller in which all relevant information is evaluated and further processed to higher and lower centres.

Role of the brain in the control of erection

In contrast to the spinal control of erection,relatively little is known about the brain control.In the present review,we have outlined the role of brain structures involved in penile erection and provided a synopsis on the brain circuit of erection.Findings from both animal and human studies are discussed.Evidence suggests that the most important structures are the frontal lobe,cingulate gyrus,amygdala,thalamus and hypothalamus.Within the brain circuit of erection,the thalamus serves as a gate-controller in which all relevant information is evaluated and further processed to higher and lower centres.

Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities

Aim: To clarify the mechanism of the therapeutic action of icariin on erectlile dysfunction (ED). Methods: PDE5 was isolated from the human platelet and PDE4 from the rat liver tissue using the FPLC system (Pharmacia, Milton Keynes, UK) and the Mono Q column. The inhibitory effects of icariin on PDE5 and PDE4 activities were investigated by the two-step radioisotope procedure with [3H]-cGMP/[3H]-cAMP. Papaverine served as the control drug. Results: Icariin and papaverine showed dose-dependent inhibitory effects on PDE5 and PDE4 activities. The IC50 of Icariin and papaverine on PDE5 were 0.432 μmol/L and 0.680μmol/L, respectively and those on PDE4, 73.50 μmol/L and 3.07μmol/L, respectively. The potencies of selectivity of icariin and papaverine on PDE5 (PDE4/PDE5 of IC50) were 167.67 times and 4.54 times, respectively. Conclusion: Icariin is a cGMP-specific PDE5 inhibitor that may be developed into an oral effective agent for the treatment of ED.

Study of the efficacy of Korean Red Ginseng in the treatment of erectile dysfunction

Aim： To examine the treatment efficacy of Korean Red Ginseng （KRG） in impotent men with erectile dysfunction （ED）. Methods： A total of 60 patients presenting mild or mild to moderate ED were enrolled in a double-blind, placebo-controlled study in which the efficacies of KRG and a placebo were compared. The patients received either 1 000 mg （3 times daily） of KRG or a placebo. Results： The five-item version of the International Index of Erectile Function （IIEF-5） score after the treatment was significantly higher in the KRG group compared with that before the treatment （from 16.4±2.9 to 21.0±6.3, P 〈 0.0001）. In contrast, there was no difference before and after the treatment in the placebo group （from 17.0±3.1 to 17.7±5.6, P 〉 0.05）. In the KRG group, 20 patients （66.6%）, reported improved erection, significant in the global efficacy question （P 〈 0.01）; in the placebo group there was no significance. Scores on questions 2 （rigidity）, 3 （penetration）, 4 and 5 （maintenance）, were significantly higher for KRG than those for the placebo when those questions were answered after 12 weeks of each treatment （P 〈 0.01）. When the score in the KRG group was compared to the placebo group after the treatment, there was a significant improvement in total score （IIEF-5 score） in questions 3 and 5 for the KRG-treated group （P 〈 0.001 and P 〈 0.0001, respectively）. The levels of serum testosterone, prolactine and cholesterol after the treatment were not statistically significant different between the KRG and the placebo group （P 〉 0.05）. Conclusion： Our data show that KRG can be an effective alternative to the invasive approaches for treating male ED.

Recent neuroanatomical studies on the neurovascular bundle of the prostate and cavernosal nerves:clinical reflections on radical prostatectomy

The neurovascular bundle of the prostate and cavernosal nerves have been used to describe the same structure ever since the publication of the first studies on the neuroanatomy of the lower urogenital tract of men, studies that were prompted by postoperative complications arising from radical prostatectomy. In urological surgery every effort is made to preserve or restore the neurovascular bundle of the prostate to avoid erectile dysfunction （ED）. However, the postoperative potency rates are yet to be satisfactory despite all advancements in radical prostatectomy technique. As the technology associated with urological surgery develops and topographical studies on neuroanatomy are cultivated, new observations seriously challenge the classical teachings on the topography of the neurovascular bundle of the prostate and the cavernosal nerves. The present review revisits the classical and most recent data on the topographical anatomy of the neurovascular bundle of the prostate prostatectomy techniques.

Recent advancement in diagnosis of vasculogenic impotence

Several dynamic tests with vasoactive drags are available for evaluating penile vascular inflows and outflows,ranging from simple pharmacologic test to more invasive radiologic sets. However, there is still no perfect single testto reflect the penile vascular flow. All possible efforts should be exerted to get the greatest erectile effect to avoid anunderestimation of blood flow to the corpora due to incomplete relaxation of the trabecular smooth muscle.Appreciation of the type and frequency of anatomical variations and potential collateral routes is important in interpretingpenile arterograms and in evaluating the hemodynamic significance of suspected arterial disease. Choice of the vasculartests should always depend on the purpose of testing.

Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet-induced obese rats

Aim： To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5 （PDE5） inhibitor, on penile erection in obese rats. Methods： The rats were fed a high-energy diet for 12 weeks and divided into three groups： an obesity-resistant （OR） control group, an obesity-prone （OP） control group, and an OP-DA-8159 treatment （DA-8159） group. The electrostimulation-induced erectile responses were measured in all groups. The body weight, plasma cholesterol, triglyceride and glucose levels were also measured. Results： In the OP control group, the maximum intracavernous pressure （ICP） and ICP/blood pressure （ICP/BP） ratio after electric stimulation were significantly lower than those in OR control group. The corresponding area under the curve （AUC） of the ICP/BP ratio, the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group, but this difference was not significant. The body weight gain, plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159, a significant increase in the maximum ICP and the ICP/BP ratio were observed. The corresponding AUCs in the DA-8159 group were also higher than those in the two control groups. Furthermore, the detumescence time was significantly prolonged after treatment with DA-8159. Conclusion： These results demon- strate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction （ED） can be improved by the treatment with DA-8159, indicating DA-8159 might be a treatment option for ED associated with obesity.

Effects of ethanol on the tonicity of corporal tissue and the intracellular Ca^2＋ concentration of human corporal smooth muscle cells

Heavy alcohol consumption is associated with an increased risk of erectile dysfunction （ED）; however, the acute effects of ethanol （EtOH） on penile tissue are not fully understood. We sought to investigate the effects of EtOH on corporal tissue tonicity, as well as the intracellular Ca^2＋ concentration （[Ca^2＋]i） and potassium channel activity of corporal smooth muscle. Strips of corpus cavernosum （CC） from rabbits were mounted in organ baths for isometric tension studies. Electrical field stimulation （EFS） was applied to strips precontracted with 10 μmol L^-1 phenylephrine as a control. EtOH was then added to the organ bath and incubated before EFS. The [Ca^2＋]i levels were monitored by the ratio of fura-2 fluorescence intensities using the fura-2 loading method. Single-channel and whole-cell currents were recorded by the conventional patch-clamp technique in short-term cultured smooth muscle cells from human CC tissue. The corpus cavernosal relaxant response of EFS was decreased in proportion to the concentration of EtOH. EtOH induced a sustained increase in [Ca^2＋]i in a dose-dependent manner, Extracellular application of EtOH significantly increased whole-cell K^＋ currents in a concentration-dependent manner （P 〈 0.05）. EtOH also increased the open probability in cell-attached patches; however, in inside-out patches, the application of EtOH to the intracellular aspect of the patches induced slight inhibition of Ca^2＋-activated potassium channel （KCa） activity. EtOH caused a dose-dependent increase in cavemosal tension by alterations to [Ca^2＋]i. Although EtOH did not affect KCa channels directly, it increased the channel activity by increasing [Ca^2＋]i. The increased corpus cavemosal tone caused by EtOH might be one of the mechanisms of ED after heavy drinking.

Roles of dopaminergic receptors in bladder and erectile function at the spinal level

1 Introduction At the spinal level, the dopaminergic, the α1adrenergic and the neurokinin receptors play definite roles in the micturition control. From the anatomical point of view, the spinal center of micturition is located close to the center of erectile function. Recently, apomorphine is used for the treatment of erectile dysfunction and its mechanism of action is considered to be mainly through the central nervous system. 2 Dopaminergic receptors and bladder function at the spinal level

Erectile potentials of a new phosphodiesterase type 5 inhibitor,DA-8159,in diet-induced obese rats

Aim:To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159,a new phosphodiesterase type 5(PDE5)inhibitor,on penile erection in obese rats.Methods:The rats were fed a high-energy diet for 12 weeks and divided into three groups:an obesity-resistant(OR)control group,an obesity- prone(OP)control group,and an OP-DA-8159 treatment(DA-8159)group.The electrostimulation-induced erectile responses were measured in all groups.The body weight,plasma cholesterol,triglyceride and glucose levels were also measured.Results:In the OP control group,the maximum intracavernous pressure(ICP)and ICP/blood pressure(ICP/BP)ratio after electric stimulation were significantly lower than those in OR control group.The corresponding area under the curve(AUC)of the ICP/BP ratio,the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group,but this difference was not significant.The body weight gain,plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159,a significant increase in the maximum ICP and the ICP/BP ratio were observed.The coerrsponding AUCs in the DA-8159 group were also higher than those in the two control groups.Furthermore,the detumescence time was significantly prolonged after treatment with DA-8159.Conclusion:These results demon- strate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction(ED)can be im- proved by the treatment with DA-8159,indicating DA-8159 might be a treatment option for ED associated with obesity.

Implantation of AMS 700 LGX penile prosthesis preserves penile length without the need for penile lengthening procedures

Implantation of an inflatable penile prosthesis （IPP） is a well-established definitive solution for erectile dysfunction when conservative treatments fail. Penile implants may shorten the penis. The AMS 700 LGX IPP is in common use but reports on its mechanical reliability, medium-term postsurgical patient satisfaction, and mean penile length preservation are lacking. We investigate the mean penile length, mechanical reliability, and patient satisfaction at 6 and 12 months after implantation of the AMS 700 LGX. This prospective study consecutively enrolled men undergoing first-time IPP implant surgery from February 2009 to April 2012. Stretched flaccid penile length, penile length at 50% and 100% of stiffness （PSO and P100） and International Index of Erectile Function （IIEF） and Erectile Dysfunction Inventory of Treatment Satisfaction （EDITS） scores, were measured at 6 and 12 months postsurgery. Of 45 patients who underwent AMS 700 LGX implantation （median age 61 years） and completed 6 months＇ follow-up, 36 （80%） completed the study. A significant difference in stretched flaccid penile length was seen between 6 and 12 months （P= 0.033）. P100 was also significantly increased at 6 and 12 months, with a mean 10% increase （1.3 ±0.4 cm） from baseline to 12 months. Differences in mean IIEF scores at 6 and 12 months were significant for the desired domain （P = 0.0001） and for overall satisfaction （P = 0.002）; however, mean EDITS scores at 6 and 12 months were not significantly improved. AMS 700 LGX is a powerful tool for preserving penile length in men undergoing penile prosthesis implantation.

Endovascular treatment of vasculogenic erectile dysfunction

The treatment of erectile dysfunction （ED） has been a fascination involving multiple medical specialities over the past century with urologic, cardiac and surgical experts all contributing knowledge toward this multifactorial disease. With the well-described association between ED and cardiovascular disease, angiography has been utilized to identify vasculogenic impotence. Given the success of endovascular drug-eluting stent （DES） placement for the treatment of coronary artery disease, there has been interest in using this same technology for the treatment of vasculogenic ED. For men with inflow stenosis, DES placement to bypass arterial lesions has recently been reported with a high technical success rate. Comparatively, endovascular embolization as an approach to correct veno-occlusive dysfunction has produced astonishing procedural success rates as well. However, after a thorough literature review, arterial intervention is only recommended for younger patients with isolated vascular injuries, typically from previous traumatic experiences. Short-term functional outcomes are less than optimal with long-term results yet to be determined. In conclusion, the hope for a minimally invasive approach to ED persists but additional investigation is required prior to universal endorsement.