You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 20131604 CONTRACTIONS OF PROSTATES FROM SPONTANEOUSLY HYPERTENSIVE RATS ARE EFFICIENTLY INHIBITED BY SILODOSIN Roberta Buono, Paolo Dell'Oglio, Giovanni La Croce, Fabio Benigni, Francesco Montorsi, and Petter Hedlund Roberta BuonoRoberta Buono MILAN, Italy More articles by this author , Paolo Dell'OglioPaolo Dell'Oglio MILAN, Italy More articles by this author , Giovanni La CroceGiovanni La Croce MILAN, Italy More articles by this author , Fabio BenigniFabio Benigni MILAN, Italy More articles by this author , Francesco MontorsiFrancesco Montorsi MILAN, Italy More articles by this author , and Petter HedlundPetter Hedlund Linkoping, Sweden More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.3154AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Silodosin, a highly selective α1A- AR antagonist improves lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH). Hypertension is a risk factor for BPH and LUTS. Silodosin reduce bladder dysfunction in spontaneously hypertensive rats (SHR). It is not known if silodosin has similar effect on prostate contractility in individuals with or without hypertension. We therefore compared the effects of silodosin, tamsulosin (moderate α1A and α1D selective AR antagonist) and Y27632 (Rho-kinase inhibitor) on nerve-induced contractions of prostates from SHR and Wistar-Kyoto (WKY) controls without hypertension. METHODS After ethical approval, prostate preparations from 4 month old SHR (n=10) and WKY (n=9) rats were functionally evaluated in organbaths. A Grass Polygraph and a Biopac system recorded isometric tension. Nerves were transmurally activated by electrical field stimulation (EFS) with a Grass S48 stimulator (20Hz). Concentration-response curves (0.1-100μM) for silodosin, tamsulosin, or Y27632 were determined. The pIC50 values were determined by linear interpolation. An ANOVA was used for statistical comparisons. RESULTS Resting tensions (RT), responses to 60mM potassium (K), and contractions to EFS were similar for prostate preparations from all rats. For WKY, RT, K and EFS were 1.2±0.1, 0.21±0.03, and 0.10±0.02 mN. Corresponding values were 1.4±0.1, 0.22±0.03, and 0.12±0.02 mN for SHR. All the investigated drugs concentration-dependently inhibited EFS-induced contractions of prostate preparations from WKY and SHR with maximal inhibitory activities (Emax) at 100μM. For silodosin, Emax was 76±8% (p<0.05 vs Y27632) and 94±8% (p<0.05 vs tamsulosin) in prostate preparations from WKY and SHR, respectively. In comparison, Emax for tamsulosin was 44±8% in WKY and 42±5% in SHR (both p<0.05 vs silodosin and Y27632). Y27632 reduced EFS contractions by 90±9% (p<0.05 vs silodosin and tamsulosin) in WKY and 93±5% in SHR (p<0.05 vs WKY). The pIC50 values were similar for the three drugs in prostate preparations from WKY. In SHR prostate preparations, the pIC50 were 5.4±0.3 (silodosin), 5.3±0.2 (Y27632), and >4 (tamsulosin; p<0.05). CONCLUSIONS Silodosin and Y27632 have equal potency and efficacy to inhibit contractions of SHR prostate preparations. Tamsulosin is less active. Considering the uroselectivity of silodosin, the current data may suggest that this α1-AR antagonist could be a preferred choice in the treatment of BPH LUTS in patients with hypertension. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e659 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Roberta Buono MILAN, Italy More articles by this author Paolo Dell'Oglio MILAN, Italy More articles by this author Giovanni La Croce MILAN, Italy More articles by this author Fabio Benigni MILAN, Italy More articles by this author Francesco Montorsi MILAN, Italy More articles by this author Petter Hedlund Linkoping, Sweden More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...