Function Of Corpus Cavernosum Research Articles

Extracellular vesicles from human urine-derived stem cells merged in hyaluronic acid ameliorate erectile dysfunction in type 2 diabetic rats by glans administration.

The high prevalence of erectile dysfunction (ED) in patients with type 2 diabetes mellitus (DM2) is a challenging clinical problem. Researches on extracellular vesicles from urine-derived stem cells (USC-EVs) have shown that they have significant therapeutic effects in a variety of diseases by injection including ED. Hyaluronic acid (HA) is especially useful for delivering bioactive molecules. This study investigated the effects and related mechanisms of local administration of human USC-EVs combined with HA (USC-EVs-HA) on a rat model of DM2ED. UCSs were extracted from human urine samples and identified for preparation of the corresponding USC-EVs. The effects of high glucose and USC-EVs on human umbilical vein endothelial cells (HUVECs) were assessed in vitro using a CCK-8 assay to determine cell proliferation and pick the most appropriate concentration for subsequent experiments. Scratch and tube formation assays were performed to assess the function of HUVECs. Quantitative real-time polymerase chain reaction (PCR) was used to detect the expression of genes such as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (BAX), and superoxide dismutase-2 (SOD2). HA, USC-EVs, and USC-EVs-HA were prepared at concentrations and then administered topically to DM2ED rats multiple times. Intracavernous pressure and mean arterial pressure were measured to assess erectile function in rats. Masson, Tunel, Immunohistochemistry, and Western blot analysis were performed to assess the fibrosis and endothelial function in corpus cavernosum, respectively. Compared with the control group, the proliferation, migration ability, and tube-forming ability of HUVECs decreased in high glucose environment, while USC-EVs could optimize the function of HUVECs, reverse the expression of apoptotic genes, and enhance the antioxidant capacity. USC-EVs-HA showed improvement in ED compared to the HA and USC-EVs groups, and the 10-dose group was better than the 5-dose group. Histologically, the USC-EVs-HA group significantly improved apoptosis, angiogenesis, and smooth muscle regeneration in the corpus cavernosum compared to the HA group. The topical application of USC-EVs-HA in the treatment of DM2ED rats has been proved effective. The potential mechanism might to promote the proliferation of endothelial cells and smooth muscle in the corpus cavernosum, which leads to the remodeling of erectile function. And multiple dosing at intervals may make the effect more pronounced.

The Impact of Long‐Duration Exposure to Microgravity and Galactic Cosmic Radiation on Corpus Cavernosum Function

During spaceflight missions, astronauts are exposed to an extreme environment with high levels of radiation and microgravity, which negatively influence the cardiovascular system. With an increased development in space exploration and growing interest in manned missions to mars, it is of high importance to evaluate the health risks associated with long‐duration spaceflights. The increased risk of oxidative stress and inflammatory damage post‐spaceflight has been associated with cardiovascular dysfunction, but little is known about the influence of space exposure on erectile function, which is a critical component for quality of life in men. The purpose of this investigation was to determine the influence of long‐duration spaceflight on corpus cavernosum (CC) function. 86 adult male Sprague‐Dawley rats were randomized into 6 different groups with half of them enduring 4‐weeks of hindlimb unloading (HLU), and exposed to sham, 0.75Gy or 1.5Gy of simulated galactic cosmic radiation at the Ground‐based GCR Simulator at the NASA Space Radiation Laboratory (NSRL). Following a 6–9‐month recovery the rats were sacrificed, and CC tissue segments were harvested and mounted into a muscle strip myograph system for ex vivo functional assessment. CC reactivity to six 10‐s,30V‐electric field stimulations with progressive frequencies in the range of 1‐32 Hz targeting the non‐adrenergic non‐cholinergic (NANC) stimulation was assessed. The effects of HLU and radiation were determined by two‐way repeated measures ANOVA. High levels of radiation significantly decreased NANC‐mediated relaxation of the CC. Treatment with nitric oxide synthase (NOS) inhibitor L‐NAME completely inhibited tissue response to electric stimulation, showing that the relaxation was mainly driven by nitric oxide. Incubation of the CC tissue with the xanthine oxidase inhibitor allopurinol, the mitochondria‐targeted antioxidant mito‐TEMPO, and the superoxide dismutase (SOD) mimetic TEMPOL increased the relaxation response of the erectile tissue for the groups exposed to radiation, with little or opposite effect on the groups under no radiation exposure. Upon treatment with the Arginase inhibitor S‐(2‐boronoethyl)‐l‐cysteine (BEC), CC tissue for the groups under radiation exposure showed a significant improvement in relaxation under NANC electric field stimulation. Comparably, western blot analysis showed increased levels of oxidative stress and lipid peroxidation in the corpus cavernosum on the groups under radiation exposure by assessment of 4‐hydroxynonenal (HNE), as well as higher levels of arginase 1 and 2. This information suggests that increased oxidative stress from radiation exposure in long spaceflight trips impairs corpus cavernosum vasoreactivity and exposes new factors to consider with space exploration to ensure that astronauts can return to normal life after long trips in space.

Evaluation of some prostaglandins modulators on rat corpus cavernosum in-vitro: Is relaxation negatively affected by COX-inhibitors?

IntroductionProstaglandins (PGs) play an important role in corpus cavernosum relaxation, as evidenced by alprostadil being used as a drug for erectile dysfunction. Reports about the effect of cyclooxygenase (COX) inhibitors on erectile function are highly contradictory. AimTo compare the potential effects of some COX inhibitors with varying COX-1/COX-2 selectivities (indomethacin, ketoprofen and diclofenac) with that of the selective COX-2 inhibitor (DFU) on corpus cavernosal tone in-vitro. The role played by PGE1, PGI2-analogue and PGE4 receptor (EP4)-agonist in controlling corpus cavernosum function and the modulation of their action by sildenafil is also studied. MethodsOrgan bath experiments were performed using isolated rat corpus cavernosum. Direct relaxations and changes to electric field stimulation (EFS, 2–16 Hz, 60 V, 0.8 ms, 10 s train)-induced relaxation by the effect of the selected drugs were studied. Strips were precontracted using phenylephrine (PE, 10−5 M). Results are expressed as mean ± SEM of 5–9 rats. ResultsAlprostadil, iloprost and L902688 (selective EP4 agonist) induced direct relaxation where L902688 showed greater relaxant effect. Sildenafil potentiated the Emax of alprostadil and iloprost but not L902688. EFS and acetylcholine (ACh)-induced relaxations were significantly potentiated in presence of indomethacin, ketoprofen and diclofenac (20, 100 μM) but not in presence of selective COX-2 inhibitor (DFU, 1 μM). GR32191B (Thromboxane A2 receptor antagonist, 10−6 M) significantly reduced the potentiatory effect of indomethacin. Only diclofenac succeeded to potentiate sodium nitroprusside (SNP)-induced relaxation. ConclusionsEP4 receptors may play an important nitric oxide (NO)/cGMP-independent role in corpus cavernosal relaxation. Nonselective COX inhibitors seem of no harm concerning cavernosal tissue relaxation, possibly because they inhibit the synthesis of the highly contracting mediator thromboxane A2.

PS-04-002 Activation of Nrf2 improves endothelial function in corpus cavernosum from aged rats and in corpus cavernosum and penile arteries from ED patients

PS-04-002 Activation of Nrf2 improves endothelial function in corpus cavernosum from aged rats and in corpus cavernosum and penile arteries from ED patients

1120 - Activation of Nrf2 improves endothelial function in corpus cavernosum from aged rats and in corpus cavernosum and penile arteries from ED patients

1120 - Activation of Nrf2 improves endothelial function in corpus cavernosum from aged rats and in corpus cavernosum and penile arteries from ED patients

Castration impairs erectile organ structure and function by inhibiting autophagy and promoting apoptosis of corpus cavernosum smooth muscle cells in rats.

The aim of this study was to determine the changes and underlying mechanisms of erectile organ structure and function in castrated rats. In addition, the regulatory effects of an androgen on autophagy and apoptosis in corpus cavernosum smooth muscle cells (CCSMCs), especially the regulatory effect of androgen on the BECN 1-Bcl-2 interaction, were investigated. Male Sprague-Dawley rats were divided into three groups (30/group): control group, castration group, and castration with testosterone supplementation group. The erectile function was examined both in vivo and in vitro, by electric stimulation of the cavernous nerve and corpus cavernosum strip bath test, respectively. Transmission electron microscopy, TUNEL assay, Masson's trichrome staining, immunohistochemistry, and western blotting were performed to determine the levels of autophagy and apoptosis, and the structural changes in corpus cavernosum. Compared with control group, the castration group showed (1) lower erectile function: lower intracavernosal pressure/mean arterial pressure ratio, lower systolic and diastolic capability of corporal strips, and reduced expressions of eNOS and nNOS; (2) greater fibrosis: decreased smooth muscle/collagen ratio, lower expression of α-SMA, and higher expression of TGF-β1; (3) inhibited autophagy: decreased autophagosomes, lower expressions of BECN1 and LC3-II; and (4) enhanced apoptosis: higher apoptotic index and decreased Bcl-2/Bax ratio. Testosterone supplementation partially improved the effects of castration. Castration attenuates erectile function and induces corporeal fibrosis by inhibiting autophagy and promoting apoptosis of CCSMCs in rats. Therefore, our study highlights the important role of androgens in maintaining the integrity of the structure and function of corpus cavernosum in rats through counter-regulation of autophagy and apoptosis, mainly by regulating BECN 1-Bcl-2 interaction.

The effect of long-term oral tadalafil treatment on corpus cavernosum function in an experimental spinal cord transection rat model

The aim of this study was to investigate the pharmacological effects of long-term oral tadalafil treatment on the corpus cavernosum function in rats subjected to experimental spinal cord transection (SCT). Thirty young adult, male Sprague–Dawley rats were randomly divided into five groups (n¼ 6, each), as follows: (1) Control,(2) Control surgery (Sham), (3) Tadalafil (Td), (4) Experimental SCT, and (5) SCT + Tadalafil (SCT + Td). SCT rat model: after removal of T8-T9 spinal processes and laminates, a full-thickness scalpel incision was made in the spinal cord. SCT + Td rat model:rats subjected to SCT were given tadalafil (5mg kg(-1), p.o.) for 4 weeks. Next, the penile cavernous tissues obtained by en blocexcision were trimmed free of the surrounding tissue to isolate cavernosal smooth muscle strips, which were then transferred into the isolated organ baths to investigate isometric tension changes in response to various bioactive agents and electrical field stimulation (EFS). The relaxation response to acetylcholine at 0.01 mM concentration was significantly less in the SCT group compared with other groups. EFS-induced relaxation in the basal and precontracted cavernous tissue preparations was greater in the SCT + Td group than in the SCT group. This study demonstrated that long-term tadalafil administration preserves relaxation responses probably by affecting through the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway in SCT-applied rats. This treatment strategy might preserve the erectile process and prevent the SCT-induced permanent damage in the cavernosal tissue.

259 INTRACAVERNOSAL STEM CELL THERAPY COMBINED WITH ORAL TADALAFIL ADMINISTRATION PRESERVES ERECTILE FUNCTION AFTER CAVERNOUS NERVE INJURY IN RATS

You have accessJournal of UrologyStem Cell Research1 Apr 2013259 INTRACAVERNOSAL STEM CELL THERAPY COMBINED WITH ORAL TADALAFIL ADMINISTRATION PRESERVES ERECTILE FUNCTION AFTER CAVERNOUS NERVE INJURY IN RATS Juan I. Martínez-Salamanca, Mercedes Zurita, Claudio Martínez-Ballesteros, Eduardo Martínez-Salamanca, Argentina Fernández, Pedro Cuevas, Jesús Vaquero, Joaquín Carballido, Carla Costa Costa, and Javier Angulo Juan I. Martínez-SalamancaJuan I. Martínez-Salamanca Madrid, Spain More articles by this author , Mercedes ZuritaMercedes Zurita Madrid, Spain More articles by this author , Claudio Martínez-BallesterosClaudio Martínez-Ballesteros Madrid, Spain More articles by this author , Eduardo Martínez-SalamancaEduardo Martínez-Salamanca Madrid, Spain More articles by this author , Argentina FernándezArgentina Fernández Madrid, Spain More articles by this author , Pedro CuevasPedro Cuevas Madrid, Spain More articles by this author , Jesús VaqueroJesús Vaquero Madrid, Spain More articles by this author , Joaquín CarballidoJoaquín Carballido Madrid, Spain More articles by this author , Carla Costa CostaCarla Costa Costa Porto, Portugal More articles by this author , and Javier AnguloJavier Angulo Madrid, Spain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1641AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Since the treatment of erectile dysfunction secondary to radical prostatectomy still remains as an outstanding challenge, this work was aimed to evaluate the efficacy of dual targeted strategy to promote cavernosal tissue preservation using systemic PDE5 inhibition and local stem-cell therapy in a rat model of cavernous nerve (CN) injury. METHODS Bilateral CN crush injury (BCNI) was produced in anesthetized male Wistar rats. Tadalafil was orally administered at 5 mg/kg/day dose, Bone marrow-derived mesenchymal stem cells (BMSC) were obtained from donor rats and in vitro expanded and characterized before intracavernosal implantation by means of an automated microinjector pump. Ex vivo function of corpus cavernosum (CC) and In vivo intracavernosal pressure (ICP) responses to CN electrical stimulation (CNES) were evaluated 4 weeks after BCNI. Cavernosal apoptosis was determined by TUNEL assays. RESULTS In CC from BCNI rats, neurogenic contractions driven by adrenergic system were enhanced while nitrergic relaxations were markedly impaired. Oral tadalafil, BMSC or combined strategy improved neurogenic relaxations and prevented cavernosal apoptosis (Table). Relaxations of CC to carbachol or sodium nitrroprusside were not altered by BCNI or any of the treatments. BCNI resulted in marked reduction of erectile responses to CNES which were partially recovered by treatment with tadalafil or by intracavernosal implantation of BMSC. The complete recovery of erectile function was only achieved when both treatments were combined (Table). CONCLUSIONS BCNI did not impair endothelial or smooth muscle relaxation of CC but selectively blunted nitrergic relaxation which was improved by oral tadalafil and intracavernosal BMSC. Erectile function was recovered only when both therapies were combined. These results support the use of dual therapeutic approaches, cell therapy and oral PDE5 inhibitors, for recovering erectile function in patients undergoing radical prostatectomy. sham BCNI BCNI+ TAD BCNI+ BMSC BCNI+ TAD+BMSC n 9 9 5 6 5 Emax adrenergic (% of K) 102.9±34.2 214.5±25.0⁎ 117.8±38.2† 218.8±47.3 157.5±20.3 Emax nitrergic (%) 64.4±10.0 20.4±5.8⁎ 36.3±19.1 39.3±9.9 45.4±6.5† Apoptotic cells/field 1.6±0.4 15.8±0.8⁎⁎⁎ 4.0±0.7⁎††† 5.5±0.8⁎⁎††† 4.6±1.0⁎††† max ICP (% of sham) 100.0±6.3 45.9±5.7⁎⁎⁎ 76.3±11.1† 62.2±14.8⁎ 92.4±4.8†† ⁎ p< 0.05, ⁎⁎ p<0.01 ⁎⁎⁎ p<0.001 vs. sham, † p<0.05, †† p<0.01, ††† p<0.001 vs. BCNI. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e106 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Juan I. Martínez-Salamanca Madrid, Spain More articles by this author Mercedes Zurita Madrid, Spain More articles by this author Claudio Martínez-Ballesteros Madrid, Spain More articles by this author Eduardo Martínez-Salamanca Madrid, Spain More articles by this author Argentina Fernández Madrid, Spain More articles by this author Pedro Cuevas Madrid, Spain More articles by this author Jesús Vaquero Madrid, Spain More articles by this author Joaquín Carballido Madrid, Spain More articles by this author Carla Costa Costa Porto, Portugal More articles by this author Javier Angulo Madrid, Spain More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effects of buried penis on the structure and function of corpus cavernosum in a rat model

Background While the abnormal appearance of the concealed penis has been well recognized, the effect of buried penis on the structure and function of corpus cavernosum has not been well studied. To explore this issue, we established a rat model and evaluated the effect of buried penis on cavernosum weight, contents and ultrastructure of tissue, and nitric oxide synthase (NOS) activity. Methods Two hundred and ten rats were randomly divided into 3 equal cohorts for 2, 4 and 6 months study (groups A, B and C). Each group was randomly divided into buried group (n=40), control group (n=15), and normal group (n=15), respectively. Intra-purse-string suture of the root of the penis was used to establish the model. Macroscopic development was judged by measuring the weight of the corpus cavernosum. Masson's trichrome staining was performed for observing microstructure while a transmission electron microscope was used for observing ultrastructure. The NOS activity was detected by a NOS activity assay kit. Results Buried penis had no significant influence on the appearance and weight of the corpus cavernosum. Buried penis resulted in decreased smooth muscle content (P &gt;0.05 in group A, and P &lt;0.05 in groups B and C) and increased fibrous connective tissue content (P &gt;0.05 in groups A and B, and P &lt;0.05 in group C) compared with the normal and control groups. Ultrastructural abnormalities of corpus cavernosum were observed in the 6-month buried group. Moreover, there was decrease of NOS activity in groups B and C (P &lt;0.05 in group B and P &lt;0.01 in group C) when compared with the normal and control groups. Conclusion Buried penis affects the structure and function of corpus cavernosum in rats and the effect is positively correlated with the buried time, but there is no significant effect on the macroscopic development. Chin Med J 2010;123(13):1736–1740

IκB kinase 2 inhibition corrects defective nitrergic erectile mechanisms in diabetic mouse corpus cavernosum

Objectives Oxidative or glyco-oxidative stress-induced activation of the transcription factor, nuclear factor (NF)-κB, is associated with the neurovascular complications of diabetes mellitus. Antioxidant treatment has beneficial effects in diabetic patients; however, delineating a possible role for NF-κB deactivation against direct antioxidant effects has been difficult. NF-κB is negatively regulated by the inhibitor of κB (IκB) complex that, in turn, is activated by specific kinases. Thus, the aim was to investigate the effects of the IκB kinase 2 inhibitor, AS602868, on corpus cavernosum function in diabetic mice. Methods Diabetes was induced by streptozotocin; the duration was 6 weeks. Intervention AS602868 treatment (100 mg/kg/day) was given for 2 weeks after 4 weeks of untreated diabetes. Corpora cavernosum were isolated in organ baths for measurement of agonist-evoked or electrical stimulation-evoked smooth muscle tensions. Results The maximal nitrergic nerve-mediated relaxation of phenylephrine-precontracted cavernosum was reduced approximately 30% by diabetes ( P <0.001). AS602868 treatment completely reversed the deficit ( P <0.001). Maximal nitric oxide-mediated endothelium-dependent relaxation to acetylcholine was attenuated approximately 32% by diabetes ( P <0.05). This was completely restored by IκB kinase 2 inhibition ( P <0.01). Furthermore, AS602868 treatment also completely corrected ( P <0.01) an approximate 20% diabetic deficit ( P <0.001) in maximal endothelium-independent relaxation to the nitric oxide donor, sodium nitroprusside. Conclusions Inhibition of IκB kinase 2 can correct nitric oxide-dependent indexes of diabetic erectile dysfunction. This suggests that NF-κB activation is important in the development of diabetic cavernosum nitrergic neuropathy and vasculopathy.

Effect of sildenafil citrate and a nitric oxide donating sildenafil derivative, NCX 911, on cavernosal relaxation and superoxide formation in hypercholesterolaemic rabbits

Hypercholesterolaemia promotes erectile dysfunction through increased superoxide formation and negation of nitric oxide (NO) bioactivity in cavernosal tissue. The source of superoxide has not been clearly defined, however. Sildenafil (Viagra™), the standard therapy for erectile dysfunction, may also be rendered more effective by the presence of an NO donor. One drug that intrinsically fulfils this criterion is sildenafil nitrate (NCX 911), an NO donating derivative of sildenafil. The objective of this study, therefore, was to determine the source of superoxide and its effect on erectile function in corpus cavernosum from hypercholesterolaemic rabbits and to determine whether NCX 911 confers an improvement over sildenafil citrate in this model. Hypercholesterolaemia elicited an increase in superoxide formation by rabbit cavernosal tissue and a reduction of carbachol-stimulated relaxation both of which were reversed by diphenylene iodonium chloride and apocynin (NADPH oxidase inhibitors). In response to sodium nitroprusside, hypercholesterolaemia also caused an attenuation of cavernosal relaxation which was not reversed with NADPH oxidase inhibitors. Both sildenafil citrate and NCX 911 significantly reversed impaired carbachol-stimulated relaxation and inhibited superoxide formation by cavernosal tissue from hypercholesterolaemic rabbits, NCX 911 being more potent. NCX 911 also augmented cavernosal cGMP levels, an effect blocked by the guanylyl cyclase inhibitor, 1H-{1,2,4}oxadiazolo {4,3- a}quinoxalin-1-one (ODQ). These data demonstrate that hypercholesterolaemia promotes erectile dysfunction through an augmentation of superoxide derived from NADPH oxidase in cavernosal tissue. It also indicates that NO donating sildenafil may be therapeutically more beneficial than conventional sildenafil in treating erectile dysfunction with an oxidative stress-related aetiology.

Effects of the peroxynitrite decomposition catalyst, FeTMPyP, on function of corpus cavernosum from diabetic mice

Peroxynitrite, the reaction product of nitric oxide and superoxide, may contribute to vascular tissue oxidant stress in diabetes mellitus. The aim was to establish whether the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis( N-methyl-4′-pyridyl)porphyrinato iron III (FeTMPyP) could improve nitric oxide-dependent autonomic nerve and microvascular penile function in the diabetic mouse. Diabetes was induced by streptozotocin; duration was 6 weeks. Intervention FeTMPyP treatment (25 mg kg −1 day −1) was given for 2 weeks following 4 weeks untreated diabetes. Corpus cavernosum were isolated in organ baths for measurement of agonist or electrical stimulation-evoked nerve-mediated tension responses. Maximum nitrergic nerve-mediated relaxation of phenylephrine-precontracted cavernosum was approximately 35% reduced by diabetes; FeTMPyP treatment reversed this deficit by 45%. The concentration response-curve for nitric oxide-mediated endothelium-dependent relaxation to acetylcholine was attenuated by diabetes; FeTMPyP restored the deficit to the nondiabetic range. Sensitivity (EC 50) to the nitric oxide donor, sodium nitroprusside, was reduced by approximately 0.56 log 10 M units in diabetes; however, FeTMPyP treatment failed to significantly reverse this deficit. Therefore, the peroxynitrite mechanism contributes to nitric oxide-dependent diabetic autonomic neuropathy and vasculopathy and may be a potential target for clinical trials using peroxynitrite decomposition catalysts.

Involvement of beta 3-adrenergic receptor activation via cyclic GMP- but not NO-dependent mechanisms in human corpus cavernosum function.

The beta(3)-adrenoreceptor plays a major role in lipolysis but the role and distribution of beta(3)-receptors in other specific sites have not been extensively studied. beta(3)-adrenergic receptors are present not only in adipose tissue but also in human gall bladder, colon, prostate, and skeletal muscle. Recently, beta(3)-adrenergic receptor stimulation was shown to elicit vasorelaxation of rat aorta through the NO-cGMP signal transduction pathway. Here we show that beta(3)-receptors are present in human corpus cavernosum and are localized mainly in smooth muscle cells. After activation by a selective beta(3)-adrenergic receptor agonist, BRL 37344, there was a cGMP-dependent but NO-independent vasorelaxation that was selectively blocked by a specific beta(3)-receptor antagonist. In addition, we report that the human corpus cavernosum exhibits basal beta(3)-receptor-mediated vasorelaxant tone and that beta(3)-receptor activity is linked to inhibition of the RhoA/Rho-kinase pathway. These observations indicate that beta(3)-receptors may play a physiological role in mediating penile erection and, therefore, could represent a therapeutic target for treatment of erectile dysfunction.

A simplified in vitro preparation of the corpus cavernosum as a tool for investigating erectile pharmacology in the rat

This work describes a simple technique for the assessment of corpus cavernosum function in a species, the rat, representing a convenient model for basic research. We obtained measurable and reproducible responses to different pharmacological agents as well as to electrical field stimulation. In view of the present results we conclude that isolation of the erectile tissue together with the septum may constitute a valuable experimental tool for investigating both local erectile mechanisms and the action of drugs, in the rat corpus cavernosum. Data obtained in the presence of n-nitro- l-arginine and methylene blue further reinforce the concept that nitric oxide may be involved in the process of erection in the rats as well as in other animal species.

Pharmacological effect of ethanol on the function of rabbit corporal cavernosal tissue.

Pharmacologic and behavioral effects of alcohol on male sexual activity have long been controversial. Among the varied effects of alcohol, it has been described that ethanol reduces nitric oxide production. Appreciating the importance of nitric oxide-mediated regulation of corporal smooth muscle, this study was designed to investigate the in vitro pharmacologic effect of 1-5% ethanol on rabbit corpus cavernosum function. The results are summarized as follows. In isolated organ bath experiments, basal resting tension of corporal strips was significantly reduced with 3 and 5% ethanol exposure. Relaxation induced by field stimulation over a frequency range of 2-16 Hz was significantly decreased with 3 and 5% ethanol exposure. However, field-stimulated contraction at 32 Hz was reduced by 5% ethanol only. When corporal strips were preincubated with phenylephrine, 3 and 5% ethanol significantly inhibited field stimulated relaxation at all frequencies. Both phasic and tonic contraction induced by phenylephrine was significantly suppressed by 3 and 5% ethanol. KCl-induced contraction was decreased by 5% ethanol. ATP-induced relaxation was significantly enhanced by 1, 3 and 5% ethanol. Bethanechol-induced relaxation was significantly suppressed by 1, 3 and 5% ethanol. Direct nitroprusside-induced relaxation was not affected by any concentration of ethanol administration. These results demonstrated that ethanol had significant effects on both contraction and relaxation of rabbit corpus cavernosum. In general, corporal relaxation mediated through the acetylcholine-L-arginine-nitric oxide pathway was significantly more sensitive to ethanol than either ATP- or nitroprusside-induced relaxation.