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

Författare

  • L. Villa
  • R. Buono
  • N. Fossati
  • P. Rigatti
  • F. Montorsi
  • F. Benigni
  • Petter Hedlund

Summary, in English

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.

Publiceringsår

2013

Språk

Engelska

Sidor

230-238

Publikation/Tidskrift/Serie

British Journal of Pharmacology

Volym

169

Issue

1

Dokumenttyp

Artikel i tidskrift

Förlag

Wiley

Ämne

  • Pharmacology and Toxicology

Nyckelord

  • ureter
  • urolithiasis
  • pressure
  • in vivo
  • alpha(1A)-adrenoceptor
  • antagonist
  • uroselectivity

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1476-5381