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- Villa, LIst Science San Raffaele, Italy (author)
Effects by silodosin on the partially obstructed rat ureter in vivo and on human and rat isolated ureters
- Article/chapterEnglish2013
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- 2013-04-12
- Wiley-Blackwell,2013
- printrdacarrier
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- LIBRIS-ID:oai:DiVA.org:liu-93392
- https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-93392URI
- https://doi.org/10.1111/bph.12123DOI
- https://lup.lub.lu.se/record/3843361URI
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- Language:English
- Summary in:English
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- Funding Agencies|Urological Research Institute||Gester Foundation||Recordati SpA||
- 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 andlt; 0.05), or 1825% (P andlt; 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.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmakologi och toxikologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmacology and Toxicology hsv//eng
- ureter
- urolithiasis
- pressure
- in vivo
- alpha(1A)-adrenoceptor
- antagonist
- uroselectivity
- MEDICINE
- MEDICIN
- ureter
- urolithiasis
- pressure
- in vivo
- alpha(1A)-adrenoceptor
- antagonist
- uroselectivity
Added entries (persons, corporate bodies, meetings, titles ...)
- Buono, RIst Science San Raffaele, Italy (author)
- Fossati, NIst Science San Raffaele, Italy (author)
- Rigatti, PUniversity of Vita Salute San Raffaele, Italy (author)
- Montorsi, FIst Science San Raffaele, Italy (author)
- Benigni, FIst Science San Raffaele, Italy (author)
- Hedlund, PetterLund University,Lunds universitet,Östergötlands Läns Landsting,Linköpings universitet,Klinisk farmakologi,Hälsouniversitetet,Hospital San Raffaele, Italy,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kfar-phe (author)
- Ist Science San Raffaele, ItalyUniversity of Vita Salute San Raffaele, Italy (creator_code:org_t)
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- In:British Journal of Pharmacology: Wiley-Blackwell169:1, s. 230-2380007-11881476-5381
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