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Effects by silodosin on the partially obstructed rat ureter in vivo and on human and rat isolated ureters.
MedLine Citation:
PMID:  23373675     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: α(1) -adrenoceptor (-AR) antagonists may facilitate ureter stone passage in humans. We aimed to study effects by the α(1A) -AR selective antagonist silodosin (compared to tamsulosin and prazosin) on ureter pressures in a rat model of ureter obstruction, and on contractions of human and rat isolated ureters. EXPERIMENTAL APPROACH: After ethical approval, ureters of male rats were cannulated beneath the kidney pelvis for in vivo ureteral intraluminal recording of autonomous peristaltic pressure waves. A partial ureter obstruction was applied to the distal ureter. Mean arterial blood pressure (MAP) was recorded. Approximate clinical and triple clinical doses of the α(1) -AR antagonists were given intravenously. Effects by the α(1) -AR antagonists on isolated human and rat ureters were studied in organ baths. KEY RESULTS: Intravenous silodosin (0.1-0.3 mg kg(-1) ) or prazosin (0.03-0.1 mg kg(-1) ) reduced obstruction-induced increases in intraluminal ureter pressures by 21-37% or 18-40%, respectively. Corresponding effects by tamsulosin (0.01 or 0.03mg kg(-1) ) were 9-20%. Silodosin, prazosin, and tamsulosin reduced MAP by 10-12%, 25-26% (p<0.05), or 18-25% (p<0.05), respectively. When effects by the α(1A) -AR antagonists on obstruction-induced ureter pressures were expressed as a function of MAP, silodosin had 6 to 8-fold and 2.5 to 8- fold better efficacy than tamsulosin or prazosin, respectively. Silodosin effectively reduced contractions of both human and rat isolated ureters. CONCLUSIONS AND IMPLICATIONS: Silodosin inhibits contractions of the rat and human isolated ureters and has excellent functional selectivity in vivo to relieve pressure-load of the rat obstructed ureter. Silodosin as pharmacological ureter stone expulsive therapy should be clinically further explored.
Authors:
L Villa; R Buono; N Fossati; P Rigatti; F Montorsi; F Benigni; P Hedlund
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-4
Journal Detail:
Title:  British journal of pharmacology     Volume:  -     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.
Affiliation:
San Raffaele Scientific Institute, Urological Research Institute, Milan, Italy; Università Vita-Salute San Raffaele, Department of Urology, Milan, Italy.
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