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 ...