Effects of four different .ALPHA.1-adrenoceptor antagonists on .ALPHA.-adrenoceptor agonist-induced contractions in isolated mouse and hamster ureters

Abstract

Purpose: To compare the efficacy of the selective α1A-adrenoceptor antagonist silodosin with those of doxazosin, terazosin, and alfuzosin against α-adrenoceptor agonist-induced contractions in mouse and hamster ureters. Methods: The four α1-adrenoceptor antagonists were evaluated against norepinephrine-induced phasic contractions in mouse isolated ureteral preparations and against phenylephrine-induced sustained contractions in hamster isolated ureteral preparations using a functional experimental technique. Results: In mouse ureters, silodosin (a selective α1A-adrenoceptor antagonist), doxazosin (a nonselective α1-adrenoceptor antagonist), terazosin (a nonselective α1-adrenoceptor antagonist), and alfuzosin (a nonselective α1-adrenoceptor antagonist) all shifted the norepinephrine concentration-response curve to the right. The rank order of potencies (pKB value) was silodosin (9.47 ± 0.16) > doxazosin (8.62 ± 0.15) > terazosin (8.39 ± 0.16) > alfuzosin (8.03 ± 0.12). In hamster ureters, all four antagonists shifted the phenylephrine concentration-response curve to the right, the rank order of potencies being silodosin (10.09 ± 0.13) > doxazosin (8.22 ± 0.16) > terazosin (7.75 ± 0.15) > alfuzosin (7.70 ± 0.10). In each case, silodosin was much more potent than the other three drugs. Conclusion: In this study, silodosin suppressed both mouse and hamster ureteral contractions more potently than doxazosin, terazosin, or alfuzosin. Hence, this α1A-adrenoceptor antagonist warrants further study as a potentially very useful medication for stone passage in urolithiasis patients.

Alpha adrenergic receptors in renal pelvis and calyces: can rat models be used?

“…This was clearly demonstrated previously (2). Alpha receptors were found to be mediating ureteral contractions in rat models (3). As this was demonstrated in rat models, human researchers used this as a model before human research.…”

Silodosin in the management of lower urinary tract symptoms as a result of benign prostatic hyperplasia: who are the best candidates

“…They found that silodosin dose dependently suppressed the phenylephrine‐induced increase in intravesical ureteral pressure, but decreased the mean blood pressure only at higher doses. In contrast, naftopidil decreased mean blood pressure at the same doses as those that phenylephrine‐induced increase in intravesical ureteral pressure . Therefore, conversely to other α1‐ARs blockers, silodosin may facilitate distal ureteral stone passage without reaching potential hypotensive doses.…”

“…Kobayashi et al. compared the effects of silodosin vs. naftopidil on intraureteral pressure in anesthetised dogs . They found that silodosin dose dependently suppressed the phenylephrine‐induced increase in intravesical ureteral pressure, but decreased the mean blood pressure only at higher doses.…”

The effect of alfuzosin on renal resistive index, urinary electrolytes and β2 microglobulin levels and TGF β-1 levels of kidney tissue in rats with unilateral ureteropelvic junction obstruction

“…31 It was revealed that 10 mg/kg alfuzosin treatment of rats with erectile dysfunction and partial bladder outlet obstruction has antioxidant effect, restored NO release, and decreased sympathomimetic effecs. 12 Besides its aforementioned effect of reducing the pressure on the urinary system, it is thought that alfuzosin provides protective benefits on kidneys and the RAA system with its antioxidant efficiency and by decreasing the sympathicomimetic tonus.…”