Bilateral Cavernosal Nerve Resection Research Articles

Myostatin, a profibrotic factor and the main inhibitor of striated muscle mass, is present in the penile and vascular smooth muscle.

Myostatin is present in striated myofibers but, except for myometrial cells, has not been reported within smooth muscle cells (SMC). We investigated in the rat whether myostatin is present in SMC within the penis and the vascular wall and, if so, whether it is transcriptionally expressed and associated with the loss of corporal SMC occurring in certain forms of erectile dysfunction (ED). Myostatin protein was detected by immunohistochemistry/fluorescence and western blots in the perineal striated muscles, and also in the SMC of the penile corpora, arteries and veins, and aorta. Myostatin was found in corporal SMC cultures, and its transcriptional expression (and its receptor) was shown there by DNA microarrays. Myostatin protein was measured by western blots in the penile shaft of rats subjected to bilateral cavernosal nerve resection (BCNR), that were left untreated, or treated (45 days) with muscle-derived stem cells (MDSC), or concurrent daily low-dose sildenafil. Myostatin was not increased by BCNR (compared with sham operated animals), but over expressed after treatment with MDSC. This was reduced by concurrent sildenafil. The presence of myostatin in corporal and vascular SMC, and its overexpression in the corpora by MDSC therapy, may have relevance for the stem cell treatment of corporal fibrosis and ED.

Separate or Combined Treatments with Daily Sildenafil, Molsidomine, or Muscle‐Derived Stem Cells Prevent Erectile Dysfunction in a Rat Model of Cavernosal Nerve Damage

Long-term daily administration of phosphodiesterase type 5 (PDE5) inhibitors in the rat prevents or reverses corporal veno-occlusive dysfunction (CVOD) and smooth muscle cell (CSMC) loss and fibrosis, in both aging and bilateral cavernosal nerve resection (BCNR) models for erectile dysfunction. In the aging rat model, corporal implantation of skeletal muscle-derived stem cells (MDSC) reverses CVOD. Nitric oxide (NO) and cyclic guanosine monophosphate can modulate stem cell lineage. To investigate in the BCNR model the effects of sildenafil at lower doses, alone or in combination with MDSC or the NO donor molsidomine, on CVOD and the underlying corporal histopathology. CVOD, histological, and biochemical markers in rat corporal tissue. Methods. Rats subjected to BCNR were maintained for 45 days either untreated, or received sildenafil in the water or retrolingually at 10, 2.5, and 1.25 mg/kg/day (medium, low, and very low doses), or intraperitoneal molsidomine, or MDSC implantation into the corpora cavernosa separately or in combination. Cavernosometry evaluated CVOD. Histopathology was assessed on penile sections by Masson trichrome, immunohistochemistry for α-smooth muscle actin (ASMA), or immunofluorescence for neuronal nitric oxide synthase (nNOS)/neurofilament 70, and in fresh tissue by Western blot for various markers and picrosirius red for collagen. All treatments normalized erectile function (drop rate), and most increased the CSMC/collagen ratio and ASMA expression in corporal tissue sections, and reduced collagen content in the penile shaft. MDSC also increased nNOS and brain-derived neurotrophic factor. The combination treatment was not superior to MDSC or sildenafil given alone, and upregulated PDE5. Lowering the dose of a continuous long-term sildenafil administration still maintained the prevention of CVOD in the BCNR rat previously observed, but it was less effective on the underlying histopathology. As in the aging rat model, MDSC also counteracted CVOD, but supplementation with very low-dose sildenafil did not improve the outcome.

Sildenafil promotes neuroprotection of the pelvic ganglia neurones after bilateral cavernosal nerve resection in the rat

To determine the gene expression profile of pelvic ganglia neurones after bilateral cavernosal nerve resection (BCNR) and subsequent treatment with sildenafil in relation to neurotrophic-related pathways. Fisher rats aged 5 months were subjected to BCNR or sham operation and treated with or without sildenafil (20 mg/kg body-weight in drinking water) for 7 days. Total RNA isolated from pelvic ganglia was subjected to reverse transcription and then to quantitative reverse transcriptase-polymerase chain reaction (PCR) with the RAT-neurotrophic array. Results were corroborated by real-time PCR and western blotting. Another set of animals were injected with a fluorescent tracer at the base of the penis, 7 days before BCNR or sham operation, and were sacrificed 7 days after surgery. Sections of pelvic ganglia were used for immunohistochemistry with antibodies against neurturin, neuronal nitric oxide synthase, tyrosine hydroxylase and glial cell line-derived neurotrophic factor receptor α2. A down-regulation of the expression of neuronal nitric oxide synthase accompanied by changes in the level of cholinergic neurotrophic factors, such as neurturin and its receptor glial cell line-derived neurotrophic factor receptor α2, artemin, neurotrophin-4 and cilliary neurotrophic factor, was observed 7 days after BCNR in pelvic ganglia neurones. Treatment with sildenafil, starting immediately after surgery, reversed all these changes at a level similar to that in sham-operated animals. Sildenafil treatment promotes changes in the neurotrophic phenotype, leading to a regenerative state of pelvic ganglia neurones. The present study provides a justification for the use of phosphodiesterase 5 inhibitors as a neuroprotective agent after BCNR.

Sildenafil Promotes Smooth Muscle Preservation and Ameliorates Fibrosis Through Modulation of Extracellular Matrix and Tissue Growth Factor Gene Expression After Bilateral Cavernosal Nerve Resection in the Rat

It has been shown that phosphodiesterase type 5 (PDE5) inhibitors preserve smooth muscle (SM) content and ameliorate the fibrotic degeneration normally seen in the corpora cavernosa after bilateral cavernosal nerve resection (BCNR). However, the downstream mechanisms by which these drugs protect the corpora cavernosa remain poorly understood. To provide insight into the mechanism, we aimed to determine the gene expression profile of angiogenesis-related pathways within the penile tissue after BCNR with or without continuous sildenafil (SIL) treatment. Five-month-old Fisher rats were subjected to BCNR or sham operation and treated with or without SIL (20 mg/kg/BW drinking water) for 3 days or 45 days (N = 8 rats per group). Total RNAs isolated from the denuded penile shaft and prostate were subjected to reverse transcription and to angiogenesis real-time-polymerase chain reaction arrays (84 genes). Changes in protein expression of selected genes such as epiregulin (EREG) and connective tissue growth factor (CTGF) were corroborated by Western blot and immunohistochemistry. Genes modulated by BCNR and SIL treatment. A decreased expression of genes related to SM growth factors such as EREG, platelet-derived growth factor (PDGF), extracellular matrix regulators such as metalloproteinases 3 and 9, endothelial growth factors, together with an upregulation of pro-fibrotic genes such as CTGF and transforming growth factor beta 2 were found at both time points after BCNR. SIL treatment reversed this process by upregulating endothelial and SM growth factors and downregulating pro-fibrotic factors. SIL did not affect the expression of EREG, VEGF, and PDGF in the ventral prostate of BCNR animals. SIL treatment after BCNR activates genes related to SM preservation and downregulates genes related to fibrosis in the corpora cavernosa. These results provide a mechanistic justification for the use of SIL and other PDE5 inhibitors as protective therapy against corporal SM loss and fibrosis after radical prostatectomy.

1125 DEVELOPMENTAL TIME COURSE OF VENO-OCCLUSIVE DYSFUNCTION AFTER BILATERAL CAVERNOSAL NERVE RESECTION DETERMINED BY TELEMETRY

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research1 Apr 20111125 DEVELOPMENTAL TIME COURSE OF VENO-OCCLUSIVE DYSFUNCTION AFTER BILATERAL CAVERNOSAL NERVE RESECTION DETERMINED BY TELEMETRY Keisha K. King, Ramon Martinez, Istvan Kovanecz, Leah A. Garcia, Sateysh Sinha, Jorge N. Artaza, and Monica G. Ferrini Keisha K. KingKeisha K. King Los Angeles, CA More articles by this author , Ramon MartinezRamon Martinez Los Angeles, CA More articles by this author , Istvan KovaneczIstvan Kovanecz Torrance, CA More articles by this author , Leah A. GarciaLeah A. Garcia Los Angeles, CA More articles by this author , Sateysh SinhaSateysh Sinha Los Angeles, CA More articles by this author , Jorge N. ArtazaJorge N. Artaza Los Angeles, CA More articles by this author , and Monica G. FerriniMonica G. Ferrini Los Angeles, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.722AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cavernosal Veno-occlusive dysfunction (CVOD) which normally occurs when there is both a loss of smooth muscle cells together with an increase in fibrosis within the corpora cavernosa, can be experimentally induced by an injury to the cavernosal nerves. We examined the use of telemetric monitoring of the intracavernosal pressure as a new reliable and non invasive method to assess CVOD following bilateral cavernosal nerve resection (BCNR) in the rat. METHODS Two month-old male Fisher 344 rats (n=8) were implanted with PhysioTel PA-C40 transmitters to monitor intracavernosal pressure. 7 days after implantation, penile intracavernosal pressure (ICP) measurements were collected by telemetry over three 12 hour periods and averaged to determine basal pressures for each animal as well as the average duration and peak heights for spontaneous erections. Animals were also injected subcutaneously with apomorphine, (60μm/kg B.W.) or intracavernosally with papaverine (15 mg/ml) After determining the ICP benchmark, Animals were then subjected to BCNR and ICPs were recorded over 12 hour during 2 month period. RESULTS In control animals, recording of the basal pressure were 28.1±2.9 mmHg. The number of spontaneous erectile events in 12 hour period were 19.5±2.74. The erectile event lasted 21± 1.3 sec and the ICP for full erections were 152.71±17.1 mmHg. Apomorphine injection induce an ICP of more than 200 mmHg and intracavernosal injection of papaverine induced an increase of the ICP up to 300 mmHg. BCNR induce a decrease in the number of spontaneous erection starting at 7 days after the surgery and reaching the maximum at 30 days with a decrease of 80% in the number of spontaneous. The basal pressure dropped to 15 mmHg and the maximum icp for erection reached 80 mmHg. CONCLUSIONS BCNR induces changes in the intracavernosal pressure indicating that resulting CVOD reaches the maximum at 30 days after surgery. Telemetry is a reliable method to measure erectile function and can be used to determine the changes in the intracavernosal pressure after nerve damage at different time point on the same specimen providing more consistent physiological and behavioral data. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e452 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Keisha K. King Los Angeles, CA More articles by this author Ramon Martinez Los Angeles, CA More articles by this author Istvan Kovanecz Torrance, CA More articles by this author Leah A. Garcia Los Angeles, CA More articles by this author Sateysh Sinha Los Angeles, CA More articles by this author Jorge N. Artaza Los Angeles, CA More articles by this author Monica G. Ferrini Los Angeles, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

891 SILDENAFIL PROMOTES SMOOTH MUSCLE PRESERVATION AFTER BILATERAL CAVERNOSAL NERVE RESECTION THROUGH ACTIVATION OF ANGIOGENESIS RELATED PATHWAYS

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2010891 SILDENAFIL PROMOTES SMOOTH MUSCLE PRESERVATION AFTER BILATERAL CAVERNOSAL NERVE RESECTION THROUGH ACTIVATION OF ANGIOGENESIS RELATED PATHWAYS Fara Sirad, Istvan Kovanecz, Jorge Artaza, Jacob Rajfer, and Monica Ferrini Fara SiradFara Sirad Los Angeles, CA More articles by this author , Istvan KovaneczIstvan Kovanecz Torrance, CA More articles by this author , Jorge ArtazaJorge Artaza Los Angeles, CA More articles by this author , Jacob RajferJacob Rajfer Torrance, CA More articles by this author , and Monica FerriniMonica Ferrini Los Angeles, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1647AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We have previously demonstrated that long term treatment with PDE 5 inhibitors preserves corporal smooth muscle and ameliorates fibrotic degeneration normally seen after bilateral cavernosal nerve resection (BCNR) in rats. However, the mechanism by which these drugs promote corporal protection remains poorly understood. We aim to determine the gene expression profile of penile tissue after BCNR and the subsequent treatment with sildenafil in relation to angiogenesis related-pathways. METHODS Fisher rats were subjected to BCNR or sham operation and treated with or without sildenafil (20 mg/Kg. B.W drinking water) for 3 days (short term treatment) or for 45 days (long term treatment). RNA isolated from the penile shaft was subjected real time-PCR array with the RAT- angiogenesis array which comprises genes involved in angiogenic, fibrotic and antifibrotic pathways. We considered as significant those genes that demonstrated a ± 2.0 fold change with its respective controls. Selected genes were corroborated by western blot analysis. RESULTS Array data analysis from the comparison of sham versus BCNR for the short term treatment, revealed a decreased expression of 20 genes related to angiogenesis and tissue growth factors such as epiregulin (EREG:-2.82), metalloproteinase 3 (MMP3:-2.43), metalloproteinase 9 (MMP9: -7.49); platelet derived growth factor (PDGF:-2.43) and endothelial cell growth factor (ECGF: -2.27) among others, and an up-regulation of pro-fibrotic and anti-angiogenic genes such as connective tissue growth factor (CTGF: 3.35) and Maspin (Serpin b5: 2.77). The short term treatment with sildenafil reversed this process by up-regulating 22 genes such as EREG: 2.01, MMP 9: 3.51 among others and down regulation of CTFG: -2.01 and TGFβ: -2.00. A similar response but with more pronounced changes were observed in the long term treatment with sildenafil in comparison with BCNR. 45 days treatment with sildenafil up-regulated the expression of 28 genes related to angiogenesis such as EREG: 87.73, MMP 9: 23.51 PDGF: 12.00 and down regulated the expression of CTGF: -2.25 and PAI-3: -2.0 and hypoxia inducible factor 1 (EPAS 1: -2.00). CONCLUSIONS Short and long term treatment with sildenafil after BCNR activates genes related to smooth muscle preservation and down regulates genes related to fibrosis. These results provide a mechanistic justification for the use of sildenafil and possibly other PDE5 inhibitors as protective therapy against corporal smooth muscle loss and fibrosis after radical prostatectomy © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e348 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fara Sirad Los Angeles, CA More articles by this author Istvan Kovanecz Torrance, CA More articles by this author Jorge Artaza Los Angeles, CA More articles by this author Jacob Rajfer Torrance, CA More articles by this author Monica Ferrini Los Angeles, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Fibrosis and Loss of Smooth Muscle in the Corpora Cavernosa Precede Corporal Veno-Occlusive Dysfunction (CVOD) Induced by Experimental Cavernosal Nerve Damage in the Rat

Corporal veno-occlusive dysfunction (CVOD), which usually is associated with a loss of smooth muscle cells (SMC) and an increase in fibrosis within the corpora cavernosa, can be induced by an injury to the cavernosal nerves. The corporal tissue expresses inducible nitric oxide synthase (iNOS), presumably as an antifibrotic and SMC-protective response. We studied the temporal relationship in the corpora between the expression of iNOS, other histological and biochemical changes, and the development of CVOD, after bilateral cavernosal nerve resection (BCNR) in the rat. Rats underwent either BCNR or sham operation. Cavernosometry was performed 1, 3, 7, 15, 30, and 45 days (N = 8/groups) after surgery. Penile tissue sections were subjected to Masson trichrome staining for SMC and collagen, and immunodetection for alpha smooth muscle actin, iNOS, neuronal NOS (nNOS), endothelial NOS (eNOS), proliferating cell nuclear antigen (PCNA), and terminal transferase dUTP nick end labeling (TUNEL). Quantitative western blot analysis was done in homogenates. Time course on the development of fibrosis and CVOD. Following BCNR, CVOD was detectable 30 days later, and it became more pronounced by 45 days. In contrast, the SMC/collagen ratio in the BCNR corpora was reduced at 7 days and bottomed at 30 and 45 days, due in part to the reduction of SMC, presumably caused by an increase in apoptosis peaking at 3 days. PCNA also peaked at 3 days, but then decayed. nNOS was reduced early (3-7 days) and disappeared at 30 days, whereas eNOS was not affected. iNOS was induced at day 3, and steadily increased peaking at 30 days. CVOD develops in the BCNR rat as a result of the early loss of corporal SMC by the neuropraxia-induced apoptosis, which the initial cell replication response cannot counteract, followed by fibrosis. The time course of iNOS induction supports the antifibrotic role of iNOS.

The Case for Postoperative PDE-5 Inhibitor Drug Treatment after Radical Prostatectomy

Journal of EndourologyVol. 22, No. 9 Prostate CancerThe Case for Postoperative PDE-5 Inhibitor Drug Treatment after Radical ProstatectomyAlberto Briganti, Andrea Gallina, Andrea Salonia, Guiseppe Zanni, Andrea Cestari, Giorgio Guazzoni, Patrizio Rigatti, and Francesco MontorsiAlberto BrigantiSearch for more papers by this author, Andrea GallinaSearch for more papers by this author, Andrea SaloniaSearch for more papers by this author, Guiseppe ZanniSearch for more papers by this author, Andrea CestariSearch for more papers by this author, Giorgio GuazzoniSearch for more papers by this author, Patrizio RigattiSearch for more papers by this author, and Francesco MontorsiSearch for more papers by this authorPublished Online:23 Sep 2008https://doi.org/10.1089/end.2008.9752AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byAlleviation of post-radical prostatectomy cavernosal fibrosis: future directions and potential utility for PDE5 inhibitors16 August 2011 | Expert Opinion on Investigational Drugs, Vol. 20, No. 10Sildenafil Promotes Smooth Muscle Preservation and Ameliorates Fibrosis Through Modulation of Extracellular Matrix and Tissue Growth Factor Gene Expression After Bilateral Cavernosal Nerve Resection in the RatThe Journal of Sexual Medicine, Vol. 8, No. 4REVIEW: Utilization of Pharmacotherapy for Erectile Dysfunction Following Treatment for Prostate Cancer1 March 2010 | The Journal of Sexual Medicine, Vol. 7, No. 3 Volume 22Issue 9Sep 2008 InformationMary Ann Liebert, Inc.To cite this article:Alberto Briganti, Andrea Gallina, Andrea Salonia, Guiseppe Zanni, Andrea Cestari, Giorgio Guazzoni, Patrizio Rigatti, and Francesco Montorsi.The Case for Postoperative PDE-5 Inhibitor Drug Treatment after Radical Prostatectomy.Journal of Endourology.Sep 2008.2025-2028.http://doi.org/10.1089/end.2008.9752Published in Volume: 22 Issue 9: September 23, 2008PDF download

Long-term continuous sildenafil treatment ameliorates corporal veno-occlusive dysfunction (CVOD) induced by cavernosal nerve resection in rats

It was recently reported in the rat that vardenafil given in a continuous long-term manner was successful in preventing smooth muscle fibrosis in the penile corpora cavernosa and corporal veno-occlusive dysfunction (CVOD) that occur following bilateral cavernosal nerve resection (BCNR), a model for human erectile dysfunction after radical prostatectomy. To expand on this finding and to determine whether this effect was common to other PDE5 inhibitors, and occurred in part by stimulation of the spontaneous induction of inducible nitric oxide synthase (iNOS, also known as NOS2), male Fischer 344 rats (N=10/group) were subjected to either BCNR or unilateral cavernosal nerve resection (UCNR) and treated with sildenafil (20 mg kg(-1) day(-1)) in the drinking water daily for 45 days. Additional BCNR groups received L-NIL (6.7 mg kg(-1) day(-1)) as inhibitor of iNOS activity, with or without concurrent sildenafil administration. It was determined that sildenafil, like vardenafil, (1) prevented the 30% decrease in the smooth muscle cell/collagen ratio, and the 3-4-fold increase in apoptosis and reduction in cell proliferation, and partially counteracted the increase in collagen, seen with both UCNR and BCNR; and (2) normalized the CVOD, measured by dynamic infusion cavernosometry, induced by both BCNR and UCNR. The long-term inhibition of iNOS activity exacerbated corporal fibrosis and CVOD in the BCNR rats, but sildenafil functional effects were not affected by L-NIL. These data suggest that the salutary effects of continuous long-term PDE5 inhibitors on erectile function post-cavernosal nerve resection involve their ability to prevent the alterations in corporal histology induced by cavernosal nerve damage, in a process apparently independent from endogenous iNOS induction.

Chronic daily tadalafil prevents the corporal fibrosis and veno‐occlusive dysfunction that occurs after cavernosal nerve resection

To determine whether a long-term single daily oral dose of a longer half-life phosphodiesterase-5 (PDE5) inhibitor, tadalafil, has a similar effect to that of the shorter half-life PDE5 inhibitors sildenafil and vardenafil, and can prevent the fibrosis and resultant corporal veno-occlusive dysfunction (CVOD) occurring after cavernosal nerve (CN) injury. Male rats (10 per group) had either a sham operation, unilateral CN resection (CNR) or bilateral CNR, and were left untreated or given retrolingually 5 mg/kg per day of tadalafil. After 45 days, CVOD was assessed via cavernosometry, and the underlying corporal tissue changes were examined by immunohistochemistry and histochemistry (followed by quantitative image analysis), Western blots, and ad hoc methods. Tadalafil treatment normalized the low response to papaverine and high drop rate in the intracavernosal pressure measured by cavernosometry after CNR compared with sham-operated rats. Tadalafil also normalized the increase in penile shaft collagen content, and the reduction in corporal smooth muscle cell (SMC) content, SMC/collagen, and replication index, and improved the lower collagen III/I ratio and the increase in apoptotic index, caused by CNR, compared with sham operation. There were no effects of tadalafil on increased transforming growth factor beta1, inducible nitric oxide synthase and xanthine oxidoreductase levels. A long-term single daily dose of tadalafil prevented CVOD and the underlying corporal fibrosis in the rat caused by CN damage, as effectively as the previously reported continuous treatment with vardenafil or sildenafil, through a cGMP-related mechanism that appears to be independent of inducible nitric oxide synthase induction.

Association of vitamin D receptor (Fok‐I) polymorphism with the clinical presentation of calcium urolithiasis

To identify differential protein expression in penile tissue in a rat model of erectile dysfunction (ED) at an early stage after bilateral cavernosal nerve (CN) neurectomy, using proteomic techniques. Twelve male adult Sprague-Dawley rats were randomly divided into two equal groups, one having bilateral CN resection and one a control group. The penises were harvested 7 days after CN resection. Total protein was separated into >1250 protein spots by two-dimensional electrophoresis using pH 3-10 nonlinear immobilized pH gradient strips. Differential expression of proteins was analysed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and database searching. Thirty-two proteins were significantly changed in the denervated penis, of which 25 (including nine up-regulated and 16 down-regulated) with cytoskeletal functions, and pathophysiological functions related to energy metabolism and oxidative stress, were identified. Examples include transgelin, creatine kinase B, annexin-1 and galactin-7. The expression of several important proteins participating in pathophysiological processes of penile tissue are changed early after bilateral CN neurectomy. These changes might give new insights into the cellular and molecular mechanisms involved in neurogenic ED development, and indicate potential therapeutic targets.

Proteomic analysis of rat penile tissue in a model of erectile dysfunction after radical prostatectomy

OBJECTIVETo identify differential protein expression in penile tissue in a rat model of erectile dysfunction (ED) at an early stage after bilateral cavernosal nerve (CN) neurectomy, using proteomic techniques.MATERIALS AND METHODSTwelve male adult Sprague‐Dawley rats were randomly divided into two equal groups, one having bilateral CN resection and one a control group. The penises were harvested 7 days after CN resection. Total protein was separated into >1250 protein spots by two‐dimensional electrophoresis using pH 3–10 nonlinear immobilized pH gradient strips. Differential expression of proteins was analysed using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry and database searching.RESULTSThirty‐two proteins were significantly changed in the denervated penis, of which 25 (including nine up‐regulated and 16 down‐regulated) with cytoskeletal functions, and pathophysiological functions related to energy metabolism and oxidative stress, were identified. Examples include transgelin, creatine kinase B, annexin‐1 and galactin‐7.CONCLUSIONSThe expression of several important proteins participating in pathophysiological processes of penile tissue are changed early after bilateral CN neurectomy. These changes might give new insights into the cellular and molecular mechanisms involved in neurogenic ED development, and indicate potential therapeutic targets.

Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat

Objectives Impotence, specifically corporal veno-occlusive dysfunction (CVOD), occurs after radical prostatectomy. It results from the effects of cavernosal nerve damage, which causes smooth muscle (SM) loss and an increase in collagen within the corpora. Recent reports have suggested that long-term treatment with phosphodiesterase-5 inhibitors after radical prostatectomy may prevent such changes. We aimed to determine whether bilateral cavernosal nerve resection (BCNX) in the rat leads to CVOD and whether long-term phosphodiesterase-5 inhibition ameliorates these histologic and functional impairments. Methods Rats (n = 7 to 11/group) underwent either the sham operation, BCNX, or BCNX plus 30 mg/L vardenafil in the drinking water. Before the rats were killed 45 days later, CVOD was assessed by dynamic infusion cavernosometry. The corpora underwent histochemistry/immunohistochemistry with quantitative image analysis for SM/collagen ratio, collagen III/I ratio, alpha-SM actin, inducible nitric oxide synthase (iNOS), proliferating cell nuclear antigen, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling as a marker of apoptosis. Results Compared with the sham group, the BCNX rats demonstrated CVOD as measured by the drop rate, a 60% reduction in the SM/collagen ratio, a twofold increase in iNOS expression, and a threefold increase in intracorporeal apoptosis. Compared with the BCNX group, vardenafil increased both iNOS and proliferating cell nuclear antigen expression (SM cell replication), with normalization of the dynamic infusion cavernosometry drop rate and SM/collagen ratio. Conclusions Long-term treatment with vardenafil may prevent CVOD after radical prostatectomy by preserving SM content and inhibiting corporal fibrosis possibly by its effect on iNOS.

1061: Effect of Bilateral Cavernosal Nerve Resection on the Histological Alterations in the Penile Vascular System

You have accessJournal of UrologyDiscussed Poster, Tuesday, May 24,2005, 8:00 am - 12:00 pm1 Apr 20051061: Effect of Bilateral Cavernosal Nerve Resection on the Histological Alterations in the Penile Vascular System Hugo H. Davila, Alejandro J. Miranda-Sousa, Istvan Kovanecz, Rafael E. Carrion, Camille Miller, Raoul Salup, Nestor F. Gonzalez-Cadavid, and Jacob Rajfer Hugo H. DavilaHugo H. Davila More articles by this author , Alejandro J. Miranda-SousaAlejandro J. Miranda-Sousa More articles by this author , Istvan KovaneczIstvan Kovanecz More articles by this author , Rafael E. CarrionRafael E. Carrion More articles by this author , Camille MillerCamille Miller More articles by this author , Raoul SalupRaoul Salup More articles by this author , Nestor F. Gonzalez-CadavidNestor F. Gonzalez-Cadavid More articles by this author , and Jacob RajferJacob Rajfer More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)35217-0AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1061: Effect of Bilateral Cavernosal Nerve Resection on the Histological Alterations in the Penile Vascular System." The Journal of Urology, 173(4S), p. 288 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 288 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Hugo H. Davila More articles by this author Alejandro J. Miranda-Sousa More articles by this author Istvan Kovanecz More articles by this author Rafael E. Carrion More articles by this author Camille Miller More articles by this author Raoul Salup More articles by this author Nestor F. Gonzalez-Cadavid More articles by this author Jacob Rajfer More articles by this author Expand All Advertisement Loading ...

Expression of transforming growth factor-beta1 in penile tissue from rats with bilateral cavernosal nerve ablation.

To explore the expression of transforming growth factor-beta(1) (TGF-beta1) in penile tissue from rats after bilateral cavernosal nerve (CN) ablation, mimicking patients who have had no nerve-sparing during prostatectomy. Ten adult male rats (neurectomy group) had a bilateral CN resection aseptically under an operating microscope, with six sham-operated rats as controls. Fifteen weeks after surgery an apomorphine test was used in all rats to assess penile erection. The penile specimens were then collected and prepared for detecting the expression of TGF-beta1 by reverse transcription-polymerase chain reaction (RT-PCR), western blot and immunohistochemistry, and for quantitative analysis of the ratio of smooth muscle to collagen fibres in the corpus cavernosum with confocal microscopy. All rats in the sham-operated group but none after neurectomy had an erectile response after subcutaneous injection with apomorphine (100 micro g/kg). Immunohistochemistry, RT-PCR and western blot analyses showed a significantly higher expression of TGF-beta1 in the penile tissues after neurectomy than after sham surgery. Smooth muscle cells (fluorescing red) and collagen fibres (green autofluorescence) after paraformaldehyde fixation, were clearly identified by confocal microscopy. The fluorescence intensity expressed as the mean (sem) ratio of smooth muscle to collagen fibres in the corpus cavernosum after neurectomy was 0.265 (0.125), significantly lower than that in the sham-operated group, at 0.760 (0.196) (P < 0.01). An increased expression of TGF-beta1 in penile tissue which promotes the synthesis of collagen may be one of the important factors for the erectile dysfunction caused by bilateral CN ablation. Similar pathophysiological processes may occur in the corpus cavernosum of patients after radical prostatectomy.