MP47-10 NO/CGMP-MEDIATED RELAXATION INDUCED BY INSULIN IN HUMAN CORPUS CAVERNOSUM AND PENILE ARTERIES IS IMPAIRED IN ERECTILE DYSFUNCTION.

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2014MP47-10 NO/CGMP-MEDIATED RELAXATION INDUCED BY INSULIN IN HUMAN CORPUS CAVERNOSUM AND PENILE ARTERIES IS IMPAIRED IN ERECTILE DYSFUNCTION. Juan I. Martínez-Salamanca, José M. La Fuente, Argentina Fernández, Eduardo Martínez-Salamanca, Pepe Cardoso, Joaquín Carballido, and Javier Angulo Juan I. Martínez-SalamancaJuan I. Martínez-Salamanca More articles by this author , José M. La FuenteJosé M. La Fuente More articles by this author , Argentina FernándezArgentina Fernández More articles by this author , Eduardo Martínez-SalamancaEduardo Martínez-Salamanca More articles by this author , Pepe CardosoPepe Cardoso More articles by this author , Joaquín CarballidoJoaquín Carballido More articles by this author , and Javier AnguloJavier Angulo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1463AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives In addition to regulate glucose homeostasis, insulin has been demonstrated to influence vascular function at local level. However, the influence of insulin in human erectile tissue is not well defined. The aim of this work was to characterize the effects of insulin in human corpus cavernosum (HCC) and penile resistance arteries (HPRA) analyzing its interactions with NO/cGMP pathway and the influence of erectile dysfunction (ED). Methods HCC and HPRA were obtained from organ donors (NoED) and patients with erectile dysfunction (ED) who gave informed consent at the time of penile prosthesis implantation. HCC and HPRA were mounted in organ chambers and wire myographs, respectively, for isometric tension recording. cGMP was determined in HCC homogenates by ELISA. Results Insulin caused concentration-dependent relaxation of HCC (n=20) and vasodilation of HPRA (n=32) (pD2 7.40±0.33 and 7.21±0.32, respectively; Emax 64.0±6.1% and 59.3±5.3%, respectively). Insulin-induced relaxation of HCC was impaired in ED patients (53.0±7.4%) with respect to NoED (80.7±7.5%, p<0.01). Responses in NoED were inhibited by guanylyl cyclase inhibition with 20μM ODQ while responses in ED were potentiated by PDE5 inhibition with 30nM tadalafil. NO/cGMP contribution was confirmed by cGMP elevation (3.18±0.54 fold increase) after exposure to 1μM insulin. Involvement of endothelium was suggested by the marked difference between vasodilation in HPRA with <25% relaxation to 10μM acetylcholine (ACh) and HPRA with >40% relaxation to ACh (47.0±6.8 vs. 68.7±7.5, p<0.01). Treatment with insulin (10nM) improved endothelium-dependent relaxation in HCC, especially in ED patients with diabetes (52.3±11.5% vs. 81.1±5.4%, p<0.05). Conclusions Insulin causes human penile smooth muscle relaxations that are mediated by NO/cGMP pathway, contributed by endothelium, and impaired by the presence of ED. Insulin also participates in the regulation of endothelial function in erectile tissue. Altered regulation of penile smooth muscle tone by insulin could contribute to ED in metabolic disorders. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e522 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Juan I. Martínez-Salamanca More articles by this author José M. La Fuente More articles by this author Argentina Fernández More articles by this author Eduardo Martínez-Salamanca More articles by this author Pepe Cardoso More articles by this author Joaquín Carballido More articles by this author Javier Angulo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...