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

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