The effect of phosphodiesterase-5 inhibitor, tadalafil, on in vitro potassium chloride-induced contractions of isolated human ureteral tissue

Abstract

Introduction: Drugs causing ureteral relaxation are used for medical expulsive therapy (MET) for stones. We investigated the in vitro ability of tadalafil to cause relaxation of potassium chloride (KCl)-induced contractions of isolated human ureteral tissue.

Materials and methods: Eight grossly normal proximal ureteral tissues were collected from the radical and donor nephrectomy specimen. The standard organ bath protocol was followed. Ureteral contractions were induced with 80 mM KCl before and after exposure to tadalafil.

Results: The median amplitude and frequency of KCl-induced contractions and the median area under the contractility curve (AUCC) after exposure to 20 μM tadalafil showed significant reductions compared to that of before exposure to tadalafil (7.87 cm, 3.79/min, and 2.98 cm², respectively, versus 9.37 cm, 4.48/min, and 4.50 cm², respectively; P = 0,026, 0.008, and 0.008, respectively). After exposure to 40 μM tadalafil, the median amplitude and frequency of KCl-induced contractions and AUCC (4.50 cm, 2.56/min, and 0.92 cm², respectively) showed significant reductions compared to that of before exposure to tadalafil (7.62 cm, 3.88/min, and 3.32 cm², respectively; P = 0.008, 0.016, and 0.008, respectively). However, reductions in the parameters after exposure to 20 μM and 40 μM tadalafil were similar (P = 0.065, 0.195, and 0.130, respectively, for median amplitude, frequency, and AUCC).

Conclusion: Tadalafil reduces KCl-induced contractions of isolated human ureteral tissue in vitro. No incremental relaxations in contractions occurred by increasing the dose of tadalafil from 20 μM to 40 μM.

Figure 1

Flow diagram of important steps in the study

Figure 2

Potassium chloride-induced contractions of isolated mounted human ureteral tissue before and after exposure to 20 μM tadalafil

Graph 1

In vitro potassium chloride-induced contractility parameters of human ureter before and after exposure to 20 μM tadalafil (Is the same graph printed twice?)

Figure 3

Potassium chloride-induced contractions of isolated mounted human ureteral tissue before and after exposure to 40 μM tadalafil

Graph 2

In vitro potassium chloride-induced contractility parameters of human ureter before and after exposure to 40 μM tadalafil

Graph 3

Comparison of reduction in in vitro potassium chloride-induced contractility parameters of human ureter after exposure to tadalafil 20 μM and 40 μM