Effects by silodosin on the partially obstructed rat ureter in vivo and on human and rat isolated ureters.
OBJECTIVE
α1 -adrenoceptor (-AR) antagonists may facilitate ureter stone passage in humans. We aimed to study effects by the α1 A -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.


METHODS
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 α1 -AR antagonists were given intravenously. Effects by the α1 -AR antagonists on isolated human and rat ureters were studied in organ baths.


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 0.03 mg 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 α1 A -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
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.
Urological Research Institute, San Raffaele Scientific Institute, Milan, Italy.
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L
Villa
R
R
Buono
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N
Fossati
P
P
Rigatti
F
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Montorsi
F
F
Benigni
P
P
Hedlund
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology; D000077409:Tamsulosin; D014513:Ureter / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000473:pathology
D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; D013449:Sulfonamides; C095285:silodosin; D000077409:Tamsulosin; D011224:Prazosin