International urology and nephrology · 2026
Synergistic relaxation of ureteral smooth muscle by doxazosin and vardenafil: experimental implications for medical expulsive therapy.
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Uysal Bulent, Tumer Erbay, Kaplan Eyup, Tore Fatma, Eroglu Muzaffer, Celikaslan Hamdiye, Dokuyucu Recep
Аннотация
PURPOSE: This study aimed to investigate the relaxant effects of doxazosin (an α₁-adrenergic receptor blocker) and vardenafil (a phosphodiesterase type 5 inhibitor) on rabbit ureteral smooth muscle using an in vitro organ-bath model, and to determine whether sequential administration enhances relaxation, particularly in different ureteral segments.
METHODS: Ureteral segments (middle and distal) were obtained from 15 adult male New Zealand White rabbits and mounted in organ baths containing oxygenated Krebs-Henseleit solution at 37 °C. Each ureteral segment (middle and distal) obtained from the animals was treated as an independent experimental unit. Thus, a total of 15 middle and 15 distal ureteral segments were analyzed (n = 15 per group). Contractions were induced by 60 mmol/L KCl, and relaxation responses to doxazosin and vardenafil-applied separately or sequentially-were recorded isometrically. The degree of relaxation was expressed as a percentage of the initial KCl-induced contraction. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test.
RESULTS: Both doxazosin and vardenafil produced significant relaxation in KCl-precontracted tissues (p < 0.001). In the middle ureter, relaxation responses were 47.3 ± 3.6% for doxazosin and 33.7 ± 3.5% for vardenafil. In the distal ureter, relaxation increased to 54.6 ± 2.2% and 40.8 ± 2.2%, respectively. Sequential administration of doxazosin followed by vardenafil yielded the greatest relaxation (84.1 ± 3.9% in middle, 88.4 ± 3.1% in distal segments; p < 0.001), whereas the reverse order produced a lower but still significant response (57.4 ± 4.8% and 80.5 ± 4.4%, respectively). Overall, distal segments exhibited greater pharmacologic sensitivity than middle ones.
CONCLUSION: Doxazosin and vardenafil both exert potent relaxant effects on ureteral smooth muscle, with enhanced efficacy when administered sequentially-especially in distal segments. These findings provide mechanistic insight into the synergistic interaction between α₁-adrenergic blockade and PDE5 inhibition and support the rationale for combination therapy in facilitating distal ureteral stone passage.
METHODS: Ureteral segments (middle and distal) were obtained from 15 adult male New Zealand White rabbits and mounted in organ baths containing oxygenated Krebs-Henseleit solution at 37 °C. Each ureteral segment (middle and distal) obtained from the animals was treated as an independent experimental unit. Thus, a total of 15 middle and 15 distal ureteral segments were analyzed (n = 15 per group). Contractions were induced by 60 mmol/L KCl, and relaxation responses to doxazosin and vardenafil-applied separately or sequentially-were recorded isometrically. The degree of relaxation was expressed as a percentage of the initial KCl-induced contraction. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test.
RESULTS: Both doxazosin and vardenafil produced significant relaxation in KCl-precontracted tissues (p < 0.001). In the middle ureter, relaxation responses were 47.3 ± 3.6% for doxazosin and 33.7 ± 3.5% for vardenafil. In the distal ureter, relaxation increased to 54.6 ± 2.2% and 40.8 ± 2.2%, respectively. Sequential administration of doxazosin followed by vardenafil yielded the greatest relaxation (84.1 ± 3.9% in middle, 88.4 ± 3.1% in distal segments; p < 0.001), whereas the reverse order produced a lower but still significant response (57.4 ± 4.8% and 80.5 ± 4.4%, respectively). Overall, distal segments exhibited greater pharmacologic sensitivity than middle ones.
CONCLUSION: Doxazosin and vardenafil both exert potent relaxant effects on ureteral smooth muscle, with enhanced efficacy when administered sequentially-especially in distal segments. These findings provide mechanistic insight into the synergistic interaction between α₁-adrenergic blockade and PDE5 inhibition and support the rationale for combination therapy in facilitating distal ureteral stone passage.