807 THE EFFECT OF HYDROXYFASUDIL ON PENILE DYSFUNCTION IN THE MALE SPONTANEOUSLY HYPERTENSIVE RAT

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research (I)1 Apr 2013807 THE EFFECT OF HYDROXYFASUDIL ON PENILE DYSFUNCTION IN THE MALE SPONTANEOUSLY HYPERTENSIVE RAT Motoaki Saito, Shogo Shimizu, and Shuhei Tomita Motoaki SaitoMotoaki Saito Yonago, Japan More articles by this author , Shogo ShimizuShogo Shimizu Yonago, Japan More articles by this author , and Shuhei TomitaShuhei Tomita Yonago, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.373AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Hypertension represents a major risk factor for erectile dysfunction. Although the etiology of hypertension-induced erectile dysfunction is multifactorial and still unknown, Rho-Rho kinase pathway is one of the key factors. We investigated whether administration of hydroxyfasudil, a Rho kinase inhibitor could alternate dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle in the SHR (spontaneously hypertensive rat). METHODS Twelve-week-old male SHRs were treated with hydroxyfasudil (3 or 10 mg/kg, i.p.) once a day for 6 weeks. Wistar rats and SHRs treated with vehicle were used as age-matched controls. Penile cGMP concentrations and Rho kinase activities were determined, and penile function was estimated by organ bath studies with norepinephrine-induced contractions and acetylcholine-induced relaxations. The participation mRNA levels of eNOS and participation protein levels of eNOS and phosphorylated eNOS were investigated by quantitative real-time PCR methods and immunoblot analysis, respectively. RESULTS The SHR showed significantly decreased cGMP concentrations, increased Rho kinase activities, norepinephrine-induced hyper-contractions, and acetylcholine-induced hypo-relaxations in the penile tissue. Treatment with hydroxyfasudil significantly improved the decreased penile cGMP concentrations, the increased Rho kinase activities, the increased norepinephrine-induced contractions, and the decreased acetylcholine-induced relaxation in a dose-dependent manner. Although there were no significant differences in expression protein levels of eNOS among any of the groups, down-regulation of eNOS mRNAs as well as phosphorylated eNOS were significantly ameliorated after treatment with hydroxyfasudil. CONCLUSIONS Our data suggest that hydroxyfasudil ameliorates hypertension-associated dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle possibly via inhibition of the Rho-Rho kinase pathway and activation of NO-eNOS pathway in the SHR. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e332 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Motoaki Saito Yonago, Japan More articles by this author Shogo Shimizu Yonago, Japan More articles by this author Shuhei Tomita Yonago, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...