Mp45-12 Chronic Administration of a Limk2 Inhibitor Improves Cavernosal Veno-Occlusive Dysfunction Through Suppression of Cavernosal Fibrosis in a Rat Model of Erectile Dysfunction After Cavernosal Nerve Injury

Abstract

penile morphology in normotensive and hypertensive rats after 5-areductase inhibitors treatment.METHODS: Sixty male rats were assigned into 6 groups as following: WKY e group composed by untreated Wistar Kyoto rats (normotensive strain); WKYþD -Wistar Kyoto rats treated with dutasteride (0.5 mg/Kg/day); WKYþF -Wistar Kyoto rats treated with finasteride (5 mg/Kg/day); H -group composed by the strain of spontaneously hypertensive rats (SHR); HþD -SHR treated with dutasteride; HþF -SHR treated with finasteride. All treatments were given by gavage during 40 days after what the animals were killed and their penis were collected and processed for histomorphometrical analysis. Sections stained with hematoxylin and eosin were used to study the cross-sectional penile area, while Masson's trichrome was used for study the surface density of smooth muscle fibers, connective tissue, and sinusoidal spaces of the corpus cavernosum. The surface density of elastic system fibers was studied in Weigert's resorcin fucsin stained section. The results were compared by one-way-ANOVA with Bonferroni's post test, considering p>0.05 as significant.RESULTS: The cross-sectional penile area of normotensive animals that received dutasteride or finasteride was reduced by 39.9% and 40% in comparison to untreated normotensive animals. The connective tissue of H group was 13.7% higher than WKY, and HþD animals had an increase of 12.9% of connective tissue in comparison to untreated hypertensive animals. The sinusoidal space was reduced by 33.7% in H in comparison to WKY. In respect to the smooth muscle surface density, WKYþD showed a reduction of 26.1% in comparison to WKY, while both HþD and HþF showed reductions of 29.4 and 32.5% in comparison to untreated H. Despite no difference in the elastic system fibers surface density was observed between H and WKY, groups WKYþD, WKYþF, HþD, and HþF had an increase of 35,7%, 41,1% 82,6%, and 31,5% in comparison to WKY. Also, HþD showed a 45,8% increase in comparison to H. CONCLUSIONS: Hypertension promoted important modifications on penile structure. Both 5-a-reductase inhibitors (dutasteride and finasteride) promoted modifications in penile morphology of normotensive and hypertensive rats, although these modifications were more prominent in hypertensive animals. Dutasteride was the drug that most affected the corpus cavernosum in this rodent model.