title: Erectile response to type 5 phosphodiesterase inhibitor could be preserved with the addition of simvastatin to conventional insulin treatment in rat model of diabetes.
abstract: Enhanced RhoA/Rho-kinase pathway plays anti-erectile role and is associated with reduced response to type 5 phosphodiesterase inhibitor (PDE5I) in diabetic animals. We tested whether adjunctive simvastatin to conventional insulin treatment would restore PDE5I-induced as well as basal erectile response in diabetic rat model of erectile dysfunction. Forty 8-week-old male Sprague-Dawley rats were equally divided into four groups, (n=10) i.e. the diabetic group (D), age-matched control (C), conventional insulin treatment (I) and adjunctive simvastatin to conventional insulin treatment (S). Following 10weeks of intraperitoneal injection of streptozotocin (STZ, 35mg/kg), the group I and S received insulin (10U NPH/day) for 4weeks. Concurrently, group S received simvastatin (20mg/kg/day). Following 14weeks of diabetes induction, basal and PDE5I (intravenous mirodenafil 1mg/kg)-elicited erectile response were assessed during cavernous nerve electrostimulation. Then, penile tissues were processed for molecular assessment. Although group I failed to restore basal and PDE5I-induced erectile response, group S showed normalized erectile responses. Furthermore, group I showed improvement of only eNOS-related pathway, whereas group S effectively controlled both eNOS-related and RhoA/Rho-kinase pathway. Conclusively, adjunctive use of simvastatin to conventional insulin treatment showed more effectiveness in restoring erectile responses of diabetic rats by controlling the RhoA/Rho-kinase pathway than conventional insulin treatment alone.
authors.affiliation: Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: K
authors.initials: K
authors.lastname: Park
authors.forename: S Y
authors.initials: SY
authors.lastname: Cho
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D007172:Erectile Dysfunction / Q000188:drug therapy*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D058986:Phosphodiesterase 5 Inhibitors; D011744:Pyrimidinones; D013449:Sulfonamides; C528396:mirodenafil; D019821:Simvastatin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein