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Effects by silodosin on the partially obstructed rat ureter in vivo and on human and rat isolated ureters

Villa, L.; Buono, R.; Fossati, N.; Rigatti, P.; Montorsi, F.; Benigni, F. and Hedlund, Petter LU (2013) In British Journal of Pharmacology 169(1). p.230-238
Abstract
Background and Purpose 1-adrenoceptor (-AR) antagonists may facilitate ureter stone passage in humans. We aimed to study effects by the 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 1-AR antagonists were given intravenously. Effects by the 1-AR... (More)
Background and Purpose 1-adrenoceptor (-AR) antagonists may facilitate ureter stone passage in humans. We aimed to study effects by the 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 1-AR antagonists were given intravenously. Effects by the 1-AR antagonists on isolated human and rat ureters were studied in organ baths. Key Results Intravenous silodosin (0.10.3mgkg1) or prazosin (0.030.1mgkg1) reduced obstruction-induced increases in intraluminal ureter pressures by 2137% or 1840% respectively. Corresponding effects by tamsulosin (0.01 or 0.03mgkg1) were 920%. Silodosin, prazosin and tamsulosin reduced MAP by 1012%, 2526% (P < 0.05), or 1825% (P < 0.05) respectively. When effects by the 1A-AR antagonists on obstruction-induced ureter pressures were expressed as a function of MAP, silodosin had six- to eightfold and 2.5- to eightfold 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ureter, urolithiasis, pressure, in vivo, alpha(1A)-adrenoceptor, antagonist, uroselectivity
in
British Journal of Pharmacology
volume
169
issue
1
pages
230 - 238
publisher
The British Pharmacological Society
external identifiers
  • wos:000317679000017
  • scopus:84876265778
ISSN
1476-5381
DOI
10.1111/bph.12123
language
English
LU publication?
yes
id
9e74d447-76dc-4478-86e2-713ec66c3dd7 (old id 3843361)
date added to LUP
2013-07-01 07:01:17
date last changed
2019-02-20 05:44:28
@article{9e74d447-76dc-4478-86e2-713ec66c3dd7,
  abstract     = {Background and Purpose 1-adrenoceptor (-AR) antagonists may facilitate ureter stone passage in humans. We aimed to study effects by the 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 1-AR antagonists were given intravenously. Effects by the 1-AR antagonists on isolated human and rat ureters were studied in organ baths. Key Results Intravenous silodosin (0.10.3mgkg1) or prazosin (0.030.1mgkg1) reduced obstruction-induced increases in intraluminal ureter pressures by 2137% or 1840% respectively. Corresponding effects by tamsulosin (0.01 or 0.03mgkg1) were 920%. Silodosin, prazosin and tamsulosin reduced MAP by 1012%, 2526% (P &lt; 0.05), or 1825% (P &lt; 0.05) respectively. When effects by the 1A-AR antagonists on obstruction-induced ureter pressures were expressed as a function of MAP, silodosin had six- to eightfold and 2.5- to eightfold 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.},
  author       = {Villa, L. and Buono, R. and Fossati, N. and Rigatti, P. and Montorsi, F. and Benigni, F. and Hedlund, Petter},
  issn         = {1476-5381},
  keyword      = {ureter,urolithiasis,pressure,in vivo,alpha(1A)-adrenoceptor,antagonist,uroselectivity},
  language     = {eng},
  number       = {1},
  pages        = {230--238},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Effects by silodosin on the partially obstructed rat ureter in vivo and on human and rat isolated ureters},
  url          = {http://dx.doi.org/10.1111/bph.12123},
  volume       = {169},
  year         = {2013},
}