Vardenafil Effect on Ureteric Smooth Muscle: In Vitro Study in Porcine Model

Introduction: Phosphodiesrase type 5 inhibitors have been recently reported to induce a relaxing effect on ureteral smooth muscle. We conducted an in vitro study to elucidate the relaxing effect of various doses of vardenafil on the porcine ureter. Moreover, we propose a porcine ureter model for the evaluation of the effect of different substances on the ureter. Materials and Methods: A total number of 24 ureters were obtained by domestic pigs. The obtained ureteral specimens were immediately placed in Krebs solution. All specimens were cut into 4- to 5-mm-long tubular segments, which were mounted in 10mL vertical chambers of an organ bath system. The same specific conditions were set to the organ bath device for all specimens. The tubular segments were connected to a force/pressure transducer device. After automatic ureteral contractions with stable frequency were achieved, different doses of vardenafil (0.1, 1, and 10 mu M) were added to the bath chambers. Isometric responses of the tissues throughout the experiment were recorded and statistically analyzed. Results: The administration of vardenafil resulted in reduction of both rate and tension of the ureteral contraction regardless of the dose of vardenafil. Nevertheless, statistical analysis revealed significantly reduced ureteral contraction rate and tension when vardenafil 1 or 10 mu M was administered in comparison to the initial steady state. Conclusion: Vardenafil concentrations of 1 and 10 mu M should be considered as appropriate for ureteral relaxation. The porcine model replicates human ureteral response in vitro at least in the case of phosphodiesrase type 5 inhibitors and probably would be useful for the evaluation of other pharmaceutical agents.