2253 SILODOSIN EFFECTIVELY REDUCES PRESSURE OF THE OBSTRUCTED RAT URETER IN VIVO

Abstract

You have accessJournal of UrologyStone Disease: Evaluation & Medical Management II1 Apr 20122253 SILODOSIN EFFECTIVELY REDUCES PRESSURE OF THE OBSTRUCTED RAT URETER IN VIVO Nicola Fossati, Luca Villa, Roberta Buono, Fabio Benigni, Francesco Montorsi, Patrizio Rigatti, and Petter Hedlund Nicola FossatiNicola Fossati Milan, Italy More articles by this author , Luca VillaLuca Villa Milan, Italy More articles by this author , Roberta BuonoRoberta Buono Milan, Italy More articles by this author , Fabio BenigniFabio Benigni Milan, Italy More articles by this author , Francesco MontorsiFrancesco Montorsi 20132, Italy More articles by this author , Patrizio RigattiPatrizio Rigatti 20132, Italy More articles by this author , and Petter HedlundPetter Hedlund Milan, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2430AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Silodosin, a highly selective α1A-AR antagonist is proposed as a putative pharmacological expulsive therapy for ureter stones. The aim of the current study was to evaluate the effect of silodosin, tamsulosin and prazosin on intraureteral pressure and on blood pressure in an in vivo rat model for partial distal ureter obstruction. METHODS After ethical approval, 46 male Sprague Dawley rats (250-300 gram) were used. Under isofluran anaesthesia, saline was infused (0.4ml/hour = normal urine production in a rat) via a polyethylene (PE)-10 catheter in the left ureter beneath the kidney pelvis. The psoas muscle was sutured around the distal ureter to create a partial obstruction. The carotid artery and femoral vein were cannulated for registration of mean arterial blood pressure (MAP) and for administration of drugs. Data were recorded via a Polygraph and a Biopac system. Approximately corresponding to therapeutic and triple doses in humans, silodosin (0.1 or 0.3 mg/kg), tamsulosin (0.01 or 0.03 mg/kg), or prazosin (0.03 or 0.1 mg/kg) were given intravenously. Values are given as mean standard error of the mean. RESULTS In rats at baseline before obstruction, spontaneous peristaltic ureter pressure waves were recorded with minimum and maximum pressures of 19.7±0.7 and 37.8±1.3cmH2O, respectively. Obstruction increased minimum and maximum pressures to 43.7±1.6 and 58.6±1.7 cmH2O but had no effect on MAP that amounted to 124±3 cmH2O. Silodosin 0.1 and 0.3mg/kg reduced the minimum pressure after obstruction by 22±7 and 19±3%, respectively. Corresponding effects by tamsulosin 0.01 and 0.03mg/kg were 10±2% and 15±3% and prazosin 0.03 and 0.1mg/kg were 20±4% and 17±5%. Maximum pressure was reduced by 24±5% and 33±5% by silodosin (0.1 and 0.3mg/kg), 13±3% and 20±4% by tamsulosin (0.01 and 0.03mg/kg), and 14±4% and 21±4% by prazosin (0.03 and 0.1 mg/kg). Silodosin, tamsulosin, and prazosin reduced MAP by 11-12% (13-14cmH2O), 17-25% (21-37cmH2O; p<0.05 vs. silodosin), and 27-32% (31-39cmH2O; p<0.05 vs. silodosin). When expressed as a function of effects on MAP, silodosin was more effective (p<0.05) than tamsulosin or prazosin to reduce pressures of the rat obstructed ureter. Nerve-induced contractions of the isolated rat and human ureters were inhibited by all drugs (0.1-100μM). The order of efficacy in rat ureter was silodosin=prazosin>tamsulosin, and silodosin>prazosin=tamsulosin in human ureter. CONCLUSIONS Silodosin reduced pressure in vivo of the obstructed rat ureter with less effect on blood pressure than tamsulosin. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e909 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicola Fossati Milan, Italy More articles by this author Luca Villa Milan, Italy More articles by this author Roberta Buono Milan, Italy More articles by this author Fabio Benigni Milan, Italy More articles by this author Francesco Montorsi 20132, Italy More articles by this author Patrizio Rigatti 20132, Italy More articles by this author Petter Hedlund Milan, Italy More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...