Cavernosal Tissue Research Articles

Great Burdock Extract on Rabbit Corpus Cavernosum

Great burdock ( Arctium lappa ) is an edible vegetable that is also used as herbal medicines in many countries. Traditionally, burdock is used to slow aging, cure male impotence and in beauty care. However, the relevant mechanisms and scientific proof of its actions have not yet been elucidated. The expansion of the corpora cavernosum smooth muscle cells of the penis is the main regulating factor of erection, and the nitric oxide-soluble guanylyl cyclase-cyclic guanine monophosphate (NO-sGC-cGMP) pathway plays an important role in maintaining expansion of the corpora cavernosum. The current study aims are to investigate the effects of burdock extract on a rabbit's corpora cavernosum. The effects of burdock on the protein expression in the cavernosum tissues and smooth muscle cells were investigated, and the changes in cGMP level were determined via enzyme-linked immunosorbent assay kit analysis. Our results showed that burdock extract increased the expression of neuronal nitric oxide synthase, cGMP-dependent kinase, sGC α1 and sGC β1 in the smooth muscle cells and tissues of the corpora cavernosum, while the expression of phosphodiesterase-5 was inhibited. Additionally, cGMP levels become elevated in the smooth muscles after treatment with burdock extract. In summary, our data suggest that burdock can facilitate in the relaxation of the corpora cavernosum; however, the benefits of burdock in treating erectile dysfunction remain to be resolved.

Age-Related Morphological Changes in Smooth Muscle and Collagen Content in Human Corpus Cavernosum

Aging process has been related to erectile dysfunction (ED) possibly due to morphological changes in corpus cavernosum among many other causes. To evaluate smooth muscle and collagen content in human corpus cavernosum and to correlate it to age. Cadaveric human cavernosal tissue was collected during the period of 1 year. Morphological analysis of a whole corpus cavernosum was performed in tissue sections stained with Masson's trichromic method to differentiate smooth muscle (red) from collagen (blue) content. Analysis was performed with specialized micrographs image analysis software. Pearson's correlation test was used to establish correlation between corpus cavernosum morphology (smooth muscle and collagen content) and age. A total sample of 89 tissues from different male cadavers were analyzed. The average age of the sample was 49.2 ± 19.1 years, with a range between 14 and 90 years. There was a statistically significant inverse correlation between age and the percentage of smooth muscle content (P = 0.012), direct correlation between age and percentage of collagen content (P = 0.019), and inverse correlation between age and the ratio of smooth muscle : collagen content (P = 0.007). Age-related morphological changes in terms of smooth muscle and collagen content are observed in human corpus cavernosum as a possible contributing factor to the development of ED.

Characteristics and management of erectile dysfunction after various treatments for prostate cancer

Preface Currently, there are many wellestablished therapeutic options for early prostate cancer, and therefore, it is difficult for both urologists and patients to choose the optimal treatment. It is essential for urologists to counsel their patients according to reliable information about the advantages and disadvantages of each therapeutic option. We picked the topic for this issue, “Characteristics and management of erectile dysfunction after various treatments for prostate cancer,” because erectile dysfunction (ED) is one of the most frequent adverse events encountered in the management of prostate cancer. We invited six specialists to review each therapeutic option: radical prostatectomy, laparoscopic radical prostatectomy, robot-assisted laparoscopic radical prostatectomy, external beam radiotherapy, brachytherapy, and androgen deprivation therapy (ADT). Among these modalities, surgical interventions tend to induce a quick drop in erectile function with slow postoperative recovery. Early postoperative rehabilitation has been introduced, aiming at the early recovery of ED. On the contrary, radiation therapy tends to maintain the patient’s erectile function for a while after treatment but it gradually decreases. ADT may compromise not only the erectile function but also the libido level, and may result in significant deterioration of the patient’s quality of life. We hope these reviews will help urologists to counsel their patients with regards to decision-making in the management of early prostate cancer.

Erectile tissue molecular alterations with aging—differential activation of the p42/44 MAP Kinase pathway

Erectile dysfunction (ED) is a common problem in aged men; however, the molecular events involved in aging ED remain unclear. To better characterize the effects of aging in the penis, we evaluated cavernosal tissue remodeling capability and the downstream activation of the intracellular signaling mediator mitogen-activated protein p42/44 kinase (p42/44 MAPK). We used male Wistar rats, which were divided in groups of 2, 6, 12, 18, and 24 months old. Penile tissues were harvested and processed for protein isolation and immunohistochemical analysis. Cavernosal viability was assessed by TUNEL assay, and proliferation was analyzed by immunohistochemical detection of proliferating cell nuclear antigen (PCNA). Immunolocalization of the activated form of p42/44 MAPK was evaluated by immunofluorescence, and changes in its phosphorylation status were quantified by western blotting. p42/44 phosphorylation profile was also assessed in situ in human young and elderly cavernosal samples. With the advancement of age, experimental cavernosal tissue remodeling was affected by an age-dependent unbalance between the rate of apoptosis and proliferation, in all erectile components. Moreover, this turnover alteration was accompanied by significant modifications in the activation profile of the downstream effector p42/44 MAPK. In the youngest corporeal samples, p42/44 was mostly activated at perivascular sites, potentially mediating cell survival/proliferation. However, in elderly experimental erectile tissue, p42/44 phosphorylation shifted to trabecular fibroblasts, indicating a potential role in extracellular matrix (ECM) production. More importantly, the same differential pattern of p42/44 activation was observed in human young and aged cavernosal fragments, suggesting a distinct function of this protein with aging. We provided evidence for the first time that with the advancement of age, there is a differential activation of p42/44 MAPK in cavernosal tissue, which may promote ECM expansion and fibrosis, therefore compromising erectile function in the elderly.

Amelioration of Penile Fibrosis: Myth or Reality

Several changes have been reported to occur in the cavernosal tissue and tunica albuginea with aging. The atherosclerosis of the penis that occurs with aging causes a decrease in penile oxygen tension. A reduction in the number of smooth muscle cells (SMCs) has been demonstrated in relation to this change in oxygen tension. Changes in the ratio of penile collagen have also been observed and could explain the decrease in penile elasticity and compliance with aging. Chronic ischemia is therefore associated with fibrosis but also with nitric oxide-cGMP reduction. The sensitivity of the α-adrenoceptors on the SMCs increases with aging. Furthermore, androgen deprivation produces penile tissue atrophy, alterations in dorsal nerve structure, alterations in endothelial morphology, reductions in trabecular SM content, increases in deposition of extracellular matrix, and increases in accumulation of adipocytes in the subtunical region of the corpus cavernosum. All of these modifications can explain the prevalence of erectile dysfunction with aging. The aim of this review is to address the underlying etiology of corporal fibrosis, especially aging, cavernosal nerve damage, androgen deprivation, and tunical fibrosis. Finally, we will address the proposed amelioration and reversal of fibrosis in terms of correcting, at least partially, the relative SMC loss that occurs with aging, diabetes, or cavernosal nerve damage and its impact on prevention of erectile dysfunction-associated cavernosal fibrosis.

Use of a modified Vinsot technique for partial phallectomy in 11 standing horses

6 geldings and 5 stallions were evaluated from January 2007 through April 2009 for the following conditions requiring phallectomy: chronic paraphimosis (n = 7), squamous cell carcinoma of the penis (3), and priapism (1). None of the 7 horses with paraphimosis was able to retract the penis. Chronicity of the paraphimosis in 6 horses ranged from 2 weeks to 2 months and was unknown in the seventh horse. Horses with paraphimosis had been medically treated without success. The horse with priapism had developed the condition secondary to acepromazine administration 2 days prior to referral and was unsuccessfully treated once by intracavernosal administration of phenylephrine and irrigation of the cavernosal tissues prior to surgery. The 3 horses with squamous cell carcinoma of the penis had had the condition for 2 years and had been treated by repeated application of a cryogen or chemotherapeutic agent to the lesions. All 11 horses underwent a partial phallectomy by means of a modified Vinsot technique. Modifications to the original technique included creation of a linear urethrostomy, alteration of the location and shape of the urethrostomy, application of a latex tourniquet, concurrent castration of stallions, and use of the procedure in standing horses. The procedure was technically easy to perform, well tolerated by the horses, and cosmetically acceptable to the owners, and had minimal postoperative complications. Long-term follow-up information was obtained from owners of 10 horses a median of 454 days after surgery; 2 owners reported mild urine scalding as the only adverse effect. The modified Vinsot technique of partial phallectomy was effective and may be useful for horses that are unsuitable candidates for general anesthesia because of medical or owner financial constraints.

Cambios bioquímicos en el tejido cavernoso causados por resección unilateral del nervio cavernoso y efectos del ácido alfalipoico en estos cambios

Objective One of the most important complications of radical prostatectomy operation is erectile disfunction (ED). Oxidative stress patterns and apoptotic changes may happen in smooth muscles and endothelial cells of corpus cavernosum after neuropraxia or neurectomy. Alpha lipoic acid (ALA) shows its antioxidant properties by eliminating free radicals. In this experimental study we investigated the effects of ALA on rehabilitation of cavernosal tissue and nitric oxide synthase (NOS) containing nerve fibers on erectile tissue. Materials and methods In this study four groups were formed by inclusion of 63 adult fertile rats. Control group (n: 9), sham operation group (n: 18), 18 rats underwent unilateral neurectomy of a 5-mm. segment of the cavernous nerve (group DI) and another 18 rats group which ALA received after unilateral neurectomy (group DII). Assessments were done 3 weeks after neurectomy. Results We assessed number of NOS containing nerve fibers via nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining. According to NADPH diaphorase staining group DII significantly recovered comparing group DI (48.89±19.00 and 17.22±6.67 respectively) (p<0.05). SOD activity is reduced in both; group DI and group DII (31.42±6.06 and 40.38±4.24). Nitrite+nitrate levels were elevated significantly in both group DI and group DII (0.52±0.05 and 0.44±0.02 micromole/gr wet tissue respectively) when compared with other groups (p<0.05). There is no statistical difference between results of group DI and Group DII (p>0.05). Conclusion This study confirms that neurectomy caused decrease of intracavernous pressure and number of NOS fibers. Neurectomy and surgical trauma caused oxidative stress in rat corpus cavernosum. As a potent antioxidant ALA has positive effects on cavernosal tissue regeneration and rehabilitation by reducing oxidative stress. In this aspect, ALA may have a potential advantage in penile rehabilitation after radical prostatectomy.

Modulation of penile erection in rabbits by Mondia whitei: possible mechanism of action.

Mondia whitei root was evaluated to validate its anecdotal use and determine its possible mode of action in the management of erectile dysfunction. Rabbits were administered with daily oral doses of 100-400 mg kg(-1) crude ethanolic extract of M. whitei and sildenafil (50 mg kg(-1)) as positive control for 6 weeks. Cavernosal tissue NOS activity and levels of NO and cGMP, and NOS and PDE protein expressions were investigated. The effect of the crude extract, chloroform and petroleum ether fractions in vitro on cavernosal tissue NOS activity and levels of NO and cGMP at 0.01 and 0.10 mg g(-1) tissue were also investigated. Results indicate that the crude extract increased NOS activity by 7% at 200 mg kg(-1) with corresponding increases in NO (88%) and cGMP (480%) levels. No significant changes in these measurements were observed with the 100 and 400 mg kg(-1) doses whilst sildenafil slightly reduced them (15.9-37.5%). NOS and PDE protein expressions in test animals were not different from controls. Pre-incubation of cavernosal tissue in vitro with the crude extract of M. whitei and its chloroform fraction markedly increased NOS activity (26-132%) and levels of NO (25%) and cGMP (50-400%) at 0.01 mg g(-1) tissue but these were reduced to near control levels when their concentrations were increased to 0.10 mg g(-1) tissue whilst the petroleum ether fraction had no effect. These findings suggest that M. whitei may influence erectile function through activation/stimulation of NOS with corresponding increases in tissue NO and cGMP levels and that certain chemical constituents present in the chloroform fraction may be responsible for biological activity.

Characterization of VEGF and Angiopoietins Expression in Human Corpus Cavernosum during Aging

Erectile dysfunction (ED) is a highly prevalent and age-related disease, caused by endothelial dysfunction and impaired cavernous angiogenesis. However, cellular and molecular changes involved in erectile pathophysiology in aging male remain to be elucidated. To characterize the vascular organization, concomitantly with analysis of the expression of vascular endothelial growth factor (VEGF), Angiopoietin 1 (Ang1) and Angiopoietin 2 (Ang2) in young and aged human corpus cavernosum. Human penile fragments were removed from patients submitted to penile deviation surgery (11 cases; 58-70 years) and from potential organ donors (four cases; 18-28 years) without ED or risk factors for ED. Smooth muscle and connective tissue were assessed by Masson's trichrome staining and computer-assisted histomorphometry. Dual immunostaining for specific markers of endothelium (von Willebrand factor) and smooth muscle cell (alpha-actin), VEGF, Ang1 and Ang2 was assayed by fluorescence microscopy. Semi-quantification of expression of angiogenic factors was performed by Western blotting. Expression of VEGF and Angiopoietins in human corpus cavernosum, using a combination of histologic stainings, and molecular biology tools in order to achieve a better understanding of cavernosal tissue remodeling with aging. Aged human corpus cavernosum presented wider sinusoidal spaces, loss of muscle cell bundles, and increased connective tissue content. Ang1 was scarcely expressed in small clusters in smooth muscle cell cytoplasm with identical localization in both studied groups. VEGF expression was abundant in smooth muscle cell and its expression markedly decreased in aged tissue, contrasting with the expression of angiopoietins that increased in the aged corpus cavernosum. Immunoflourescent studies of cellular markers and growth factors help clarifying vascular organization and angiogenesis mechanisms in erectile tissue. Our findings demonstrate that the organization pattern of vascular endothelium and smooth muscle components of cavernosal tissue modifies during aging. Ang1 and Ang2 upregulation in human-aged penile tissue suggest a VEGF-independent vascular remodeling mechanism.

Increased contractile responses in corpora cavernosa of heart failure rats

IntroductionHeart failure (HF) is a risk factor for erectile dysfunction (ED). HF patients experience a decreased libido, frequency of coitus and sexual performance. The mechanisms underlying the association of HF and ED are unknown. We hypothesize that HF increases cavernosal reactivity.Methods and ResultsHF was induced, in Wistar male rats (8 week‐old), by left coronary artery ligation for 6 weeks. Ejection fraction (Sham: 85.5±3.3 vs HF: 33.9±3.0, %) and fractional shortening (Sham: 63.9±3.8 vs HF: 17.3±1.7, %) were measured to confirm the presence of HF. HF rats displayed increased cavernosal contractile responses to KCl (Sham: 0.55±0.07 vs HF: 0.82±0.06, mN/mg) and phenylephrine in the absence (Sham: 0.71±0.05 vs HF: 0.97±0.05, mN/mg) or in the presence of L‐NAME (Sham: 0.70±0.05 vs HF: 1.14±0.06, mN/mg). Sympathetic‐mediated contractile responses were increased in cavernosal strips of HF rats in the absence (Sham: 0.55±0.09 vs HF: 1.03±0.08, mN/mg) and in the presence of L‐NAME (Sham: 0.67±0.1 vs HF: 1.33±0.1, mN/mg). HF rats displayed increased cavernosal relaxation to sodium nitroprusside (Sham: 57.8±3.4 vs HF: 76.5±5.7, % of relaxation), but no changes were observed in nonadrenergic‐noncholinergic‐ (NANC)‐induced relaxation.ConclusionOur results suggest that increased contractility of the cavernosal tissue in HF rats may represent the mechanism of ED associated with HF.

874 THE REGULATION OF ANGIOTENSIN II-INDUCED CONTRACTION AND NON ADRENERGIC-NON CHOLINERGIC NEUROTRANSMISSION IN HUMAN CORPUS CAVERNOSAL TISSUE: A ROLE FOR LOSARTAN

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2010874 THE REGULATION OF ANGIOTENSIN II-INDUCED CONTRACTION AND NON ADRENERGIC-NON CHOLINERGIC NEUROTRANSMISSION IN HUMAN CORPUS CAVERNOSAL TISSUE: A ROLE FOR LOSARTAN Hani Ertemi, Faiz Mumtaz, James Bellringer, Philip Thomas, Dimitri Mikhailidis, and Cecil Thompson Hani ErtemiHani Ertemi More articles by this author , Faiz MumtazFaiz Mumtaz More articles by this author , James BellringerJames Bellringer More articles by this author , Philip ThomasPhilip Thomas More articles by this author , Dimitri MikhailidisDimitri Mikhailidis More articles by this author , and Cecil ThompsonCecil Thompson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1630AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Angiotensin II (Ang II), a vasoactive peptide, induces smooth muscle contraction and is an important regulator of systemic blood pressure. However, its influence on human corpus cavernosal smooth muscle (CCSM) function has barely been assessed. We have studied the effect Ang II has on human CCSM contractility and the influence of losartan the AT1 receptor antagonist. In addition, the interaction between Ang II and NO in modulating non adrenergic-non cholinergic neurotransmission following electrical field stimulation (EFS) was also assessed with losartan METHODS Experiments were carried out on corpus cavernosal tissue obtained from patients undergoing gender reassignment surgery, using organ baths. CCSM response to Ang II (10-8 – 10-5 M), in the absence and presence of losartan (10-5 M; AT1 receptor antagonist) were determined; together with the effect of losartan on sodium nitroprusside (SNP; NO donor)-mediated CCSM relaxation. In other experiments EFS-induce relaxation were obtained following the addition of cholinergic and cyclooxygenase inhibitors; the effect of losartan on this response was also determined RESULTS The results were expressed as a percentage of the phenylephrine 10-4 M response and showed that Ang II caused a dose dependent contraction of human CCSM strips. The Ang II contractile response was inhibited by losartan (e.g. Ang II; 10-5 M & 10-6 M were reduced by 65% & 78%; p<0.006, respectively). In addition, losartan potentiated the SNP-induced relaxation of CCSM tissue by 9% and 35% at 3x10-7M & 10-7M; p<0.04, respectively. EFS-induced relaxation of CCSM tissue at 8 Hz was also potentiated by losartan (p<0.027) CONCLUSIONS Ang II caused a profound contraction of human CCSM tissue via the activation of AT1 receptor. It is likely that Ang II and NO interact to modulate human cavernosal function, since losartan potentiated SNP- and EFS-mediated CCSM relaxation. These findings further strengthen the argument for the role of Ang II in the regulation of human penile smooth muscle tone, moreover, AT1 receptor inhibition, at least in part, may be a therapeutic approach to treat erectile dysfunction. London, United Kingdom© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byErtemi H, Mumtaz F, Howie A, Mikhailidis D and Thompson C (2018) Effect of Angiotensin II and its Receptor Antagonists on Human Corpus Cavernous Contractility and Oxidative Stress: Modulation of Nitric Oxide Mediated RelaxationJournal of Urology, VOL. 185, NO. 6, (2414-2420), Online publication date: 1-Jun-2011. Volume 183Issue 4SApril 2010Page: e342 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hani Ertemi More articles by this author Faiz Mumtaz More articles by this author James Bellringer More articles by this author Philip Thomas More articles by this author Dimitri Mikhailidis More articles by this author Cecil Thompson More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

An animal model of ischemic priapism and the effects of melatonin on antioxidant enzymes and oxidative injury parameters in rat penis

This experimental study was designed to produce ischemia-reperfusion (I/R) injury in rat corpus cavernosum by inducing 1 h of priapism and investigating the effects of melatonin on the levels of oxidative injury parameters. Twenty-one adult male rats were randomly divided into three groups as follows; sham operated, control group (Group C): only penectomy was performed and blood (3 ml) drawn from vena cava inferior (VCI), ischemia and reperfusion group (Group I/R); priapism (1 h) + ½ h reperfusion + penectomy + blood from VCI, melatonin treatment group (Group I/R + M); priapism (1 h) + melatonin (½ h before reperfusion, 50 mg/kg, ip) + ½ h reperfusion + penectomy + blood from VCI. Priapism was induced with a vacuum erection device (cut tip of 2-cc syringe) and a rubber band was placed at the base of the erect penis. In two groups, excluding Group C, penectomies were performed after 1 h of ischemic priapism and ½ h reperfusion for biochemical analysis of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and protein carbonyl (PC) in the tissues. In all groups, about 3 ml blood was drawn from VCI to study the same parameters in systemic circulation. The results were compared statistically using one-way analysis of variance (ANOVA). As a result, in biochemical examination of penile tissues, there were significant increase in SOD, CAT activities and MDA levels in I/R group in comparison with group C (P < 0.05). With melatonin treatment, these levels were decreased closer to control levels (P < 0.05). The changes in PC levels were insignificant in penile tissues of all groups (P > 0.05). Analysis of serum in all rats revealed that the activity of SOD and the levels of MDA, NO and PC were increased in I/R group when compared with control group but with multiple comparisons only the increases in SOD activity and NO level were significant (P < 0.05). Decrease in the activity of SOD and the levels of NO and PC were significant after melatonin administration in serum of all groups (P < 0.05). The results of this study showed that experimentally induced priapism caused oxidative injury in cavernosal tissues of rats, and treatment with melatonin alleviated these effects. From the result of this experimental study, it can be extrapolated that melatonin may be used as an antioxidant agent in the treatment of ischemic priapism in the future urology practice.

Pharmacological Evaluation of Ayurvedic Plants for Aphrodisiac Activity in Experimental Animals

Vajikaran Chikitsa is the branch of Ashtanga Ayurveda, which deals with all types of physical and psychological sexual problems like impotence, libido, poor erection, and early ejaculation in males. The WHO estimated that the usage of traditional medicine in developing countries is 80% and suggested a need for further exploration of the natural aphrodisiacs for the mechanism of action. Considering the prevalence of the sexual dysfunctioning in the society, side effects with the conventional aphrodisiac drugs, the study was planned to evaluate some Ayurvedic plants like Abutilon indicum and Withania somnifera for the aphrodisiac potential. An attempt was also made to elucidate the possible mechanism of action of these plants for their use in Vagikarana chikitsa. From the present study, it could be concluded that A. indicum and W. somnifera both possessed marked aphrodisiac activity complying many facets such as enhancement in libido, increase in the sexual performance, penile erection and anabolism, increased spermatogenesis as well as sperm validity. Study results pointed out the place of these drugs in the Vajikarana Chikitsa. A. indicum would be useful in management of erectile dysfunction as it had shown to relax penile cavernosal tissue probably by phosphodiesterase inhibition and cGMP accumulation.

Biochemical changes in cavernosal tissue caused by single sided cavernosal nerve resection and the effects of alpha lipoic acid on these changes

ObjectiveOne of the most important complications of radical prostatectomy operation is erectile disfunction (ED). Oxidative stress patterns and apoptotic changes may happen in smooth muscles and endothelial cells of corpus cavernosum after neuropraxia or neurectomy. Alpha lipoic acid (ALA) shows its antioxidant properties by eliminating free radicals. In this experimental study we investigated the effects of ALA on rehabilitation of cavernosal tissue and nitric oxide synthase (NOS) containing nerve fibers on erectile tissue. Materials and methodsIn this study four groups were formed by inclusion of 63 adult fertile rats. Control group (n: 9), sham operation group (n: 18), 18 rats underwent unilateral neurectomy of a 5-mm. segment of the cavernous nerve (group DI) and another 18 rats group which ALA received after unilateral neurectomy (group DII). Assessments were done 3 weeks after neurectomy. ResultsWe assessed number of NOS containing nerve fibers via nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining. According to NADPH diaphorase staining group DII significantly recovered comparing group DI (48.89±19.00 and 17.22±6.67 respectively) (p<0.05). SOD activity is reduced in both; group DI and group DII (31.42±6.06 and 40.38±4.24). Nitrite+nitrate levels were elevated significantly in both group DI and group DII (0.52±0.05 and 0.44±0.02 micromole/gr wet tissue respectively) when compared with other groups (p<0.05). There is no statistical difference between results of group DI and Group DII (p>0.05). ConclusionThis study confirms that neurectomy caused decrease of intracavernous pressure and number of NOS fibers. Neurectomy and surgical trauma caused oxidative stress in rat corpus cavernosum. As a potent antioxidant ALA has positive effects on cavernosal tissue regeneration and rehabilitation by reducing oxidative stress. In this aspect, ALA may have a potential advantage in penile rehabilitation after radical prostatectomy.

Combination of Doxazosin and Sildenafil Exerts an Additive Relaxing Effect Compared with Each Compound Alone on Human Cavernosal and Prostatic Tissue

Combination of Doxazosin and Sildenafil Exerts an Additive Relaxing Effect Compared with Each Compound Alone on Human Cavernosal and Prostatic Tissue

Changes in the neurogenic and endothelium-dependent relaxant responses of rabbit corpus cavernosum smooth muscle after cavernous nerve neurotomy

The present study was conducted to investigate the reactivity of the corpus cavernosum smooth muscle after unilateral cavernous nerve neurotomy in rabbits. Rabbits (18) were randomly divided into two groups: sham-operated (n = 9) and those subjected to unilateral neurotomy of a 5-mm segment of the cavernous nerve (n = 9). The reactivity of the corpus cavernosum tissue from the neurotomized and sham groups was studied in organ chambers at 4 weeks postoperation. In the neurotomized group, endothelium-dependent relaxation of the corpus cavernosum smooth muscle to carbachol was significantly increased when compared to the sham group. In addition, the sensitivity (i.e., pD(2)) of neurotomized strips to carbachol was also increased when compared to controls. Electrical field stimulation-induced neurogenic relaxation was significantly reduced in the neurotomized group. Relaxation to the nitric oxide (NO) donor sodium nitroprusside and to papaverine was similar in the cavernosal tissue of both groups. There was no change in agonist potency. Furthermore, neurotomy had no effect on KCl-induced contractile responses. When tissue contraction was induced with phenylephrine to study relaxation to various stimuli, the tension induced was similar in the neurotomized and the sham control groups. We conclude that unilateral, chronic cavernous nerve neurotomy causes significant functional changes to the penile erectile tissue of rabbits, which may contribute to the development of impotence.

PDE5 Inhibitors in the Treatment of LUTS

Both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) have a negative impact on patients' quality of life. The co-prescription of two active agents for these conditions will improve each condition and the addition of one drug to the other may potentiate the primary response of the first treatment and thereby improve the QoL of patients. Several epidemiological studies have indicated that the association between LUTS and ED is more than a co-incidence of age, with a possible cause and effect relationship. LUTS is more common in men with ED and there is a strong relationship between the severity of LUTS and the degree of erectile difficulty. Four pathophysiologies have been suggested to explain the relationship between LUTS and ED. There is a complex interaction between these mechanisms and there may be additional processes involved. These are: (1) alteration in nitric oxide levels; (2) autonomic hyperactivity; (3) changes in the Rho-kinase/endothelin pathway; and (4) pelvic vasculature atherosclerosis. Studies of all three easily available PDE-5 inhibitors have shown improvements in both LUTS and ED in men with significant problems in both areas without any substantial increase in side effect profile. Studies have also shown that the greatest improvements occurred with the combination of an alpha blocker and PDE-5 inhibitor when compared with either drug alone. Whilst significant improvements were seen in LUTS symptom scores, there was no significant improvement in flow rates with PDE-5 inhibitors when compared with placebo. High quality basic science studies of PDE-5 inhibitors on bladder muscle and alpha blocker agents on penile cavernosal tissue have provided several explanations for their modes of action. Even so, the mechanism of action of PDE-5 inhibitors in LUTS remains far from certain. More well-designed, placebo-controlled studies are needed to confirm the impact of these drugs, alone or in combination, on both ED and LUTS. However combination therapy appears appropriate for patients with both LUTS and ED. At present though, we should not routinely offer a combination of PDE-5 inhibitors and alpha blocker for the treatment of LUTS alone.

Erectile dysfunction and LUTS at the cellular level: Impact of Aging and/or Hypogonadism on Prostate & Cavernosal Tissues

Erectile dysfunction and LUTS at the cellular level: Impact of Aging and/or Hypogonadism on Prostate & Cavernosal Tissues

Expression of Caveolin-1 in Penile Cavernosal Tissue in a Denervated Animal Model after Treatment with Sildenafil Citrate

Radical pelvic surgery is a major cause of erectile dysfunction due to iatrogenic cavernous nerve damage. Endothelial nitric oxide synthase, which generates nitric oxide (NO) in the cavernosal tissues, localizes to specialized plasma membrane invaginations known as caveolae. Growing evidence suggests that caveolae are major components of signal trafficking and that stimuli that affect the concentration of the main structural protein of caveolae, caveolin-1 influence NO signaling. To evaluate caveolin-1 expression as a marker of cavernous tissue damage and determine the impact of early sildenafil administration on caveolin-1 expression in animal models of partial and total surgical penile denervation. Thirty-six rats were divided into six groups (N = 6 per group) that received bilateral or unilateral penile denervation or sham surgery, with and without sildenafil 10 mg daily for 7 weeks. Sections were taken from the proximal middle portion of the penis of all animals. Cavernous tissue was delineated by the tunica albuginea, then the extent of immunostaining for the following parameters was quantitated to determine (i) cavernous smooth muscle layer in the cavernous space expressed as the percentage of alpha-smooth muscle actin (alpha-SMA) positive immunostaining per area and (ii) caveolin-1 expressed as a percentage of area. A marked decrease in both caveolin-1 and alpha-SMA expression in cavernous smooth muscle tissue and in the endothelium of rats was noted after a bilateral and unilateral neurotomy. Specimens from animals receiving sildenafil exhibited higher mean immunostaining values for both proteins in cavernous tissue. The differences were statistically significant compared with groups receiving the same surgical treatment without sildenafil. Caveolin-1 and alpha-SMA expression in cavernous tissue is significantly reduced by pelvic nerve injury, and the loss is related to the extent of the neural damage. Early administration of sildenafil elicits caveolin-1 expression, which appears to preserve cavernous tissue.

Effect of hydrogen sulphide‐donating sildenafil (ACS6) on erectile function and oxidative stress in rabbit isolated corpus cavernosum and in hypertensive rats

OBJECTIVE To study the effect of the H(2)S-donating derivative of sildenafil (ACS6) compared to sildenafil citrate and sodium hydrosulphide (NaHS) on relaxation, superoxide formation and NADPH oxidase and type 5 phosphodiesterase (PDE5) expression in isolated rabbit cavernosal tissue and smooth muscle cells (CSMCs), and in vivo on indices of oxidative stress induced with buthionine sulphoximine (BSO). MATERIALS AND METHODS Relaxation was studied in an organ bath in response to carbachol and after incubation with interleukin-1beta for 12 h. CSMCs were incubated with tumour-necrosis factor-alpha or the thromboxane A(2) (TXA(2)) analogue, U46619, with or with no sildenafil citrate, ACS6 or NaHS for 16 h. Superoxide formation and the expression of p47(phox) (an active subunit of the NADPH oxidase complex) and PDE5 protein was then assessed using Western blotting. Rats were also treated with BSO (with or with no sildenafil citrate or ACS6) for 7 days; cavernosal cGMP, cAMP, glutathionine and plasma TXA(2) and 8-isoprostane F(2alpha) was measured by enzyme-linked immunosorbent assay. RESULTS ACS6 and sildenafil citrate relaxed cavernosal smooth muscle equipotently; NaHS alone had little effect at up to 100 microm. The formation of superoxide and expression of p47(phox) and PDE5 was reduced by ACS6, sildenafil citrate and NaHS (order of potency: ACS6 > sildenafil citrate > NaHS). The effects of ACS6 were blocked by inhibitors of protein kinase A (PKA) and PKG. In rats treated with BSO, both ASC6 and sildenafil citrate reduced the increased plasma levels of TXA(2) and 8-isoprostane F(2alpha) but increased cGMP, cAMP and glutathionine levels in corpus cavernosum. CONCLUSIONS By virtue of a dual action on PKA and PKG activation, ACS6 not only promotes erection, acutely, but might also have a long-term beneficial effect through inhibition of oxidative stress and downregulation of PDE5.