Presented by: Ahmet Gudeloglu
Department of Urology, Hacettepe University

Introduction

In this study, we aimed to investigate the effects of Mirabegron (MRB), a β3- adrenergic receptor agonist with current widespread clinical use in the treatment of overactive bladder disease, on isolated healthy human ureter.

Materials

The approval of review board of the ethical committee was obtained prior to the study. This prospective study was designed as series of in vitro tissue experiments. Graft kidney’s ureteral tissues of living donors who underwent surgery at our center between December 2020 and June 2021 were preferred. Informed consent was obtained from all patients. Ureters were transected harvested at the level of just above iliac crossing. Tissue transfer took place in the sealed flask containing pre-gassed Krebs solution. Ureters were eventually detubularized and stripes were suspended in organ baths. The tissue activity was recorded after stripes were left to rest until spontaneous contractions were observed. Consequently, tissue responses were recorded by adding increasing concentrations of Mirabegron. The myogenic activity was recorded via electro-mechanical transducer set-up and AcqKnowledge^® 4.2 (BIOPAC Systems, Inc.) software. Data analysis was performed with software SPSS 24.0 (IBM Corp., Chicago, USA) and GraphPad Prism 6 (GraphPad, La Jolla, CA, USA).

Results

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The total of 24 tissue strips from 16 ureters were prepared and studied. Of these, only 15 strips exhibited spontaneous or inducible activity. The effect of Mirabegron was examined in tissues with spontaneous activity. The data of strips without detectable activity was excluded from the study. It was determined that MRB lowered the frequency of spontaneous ureteric contraction in the concentration-dependent manner (Figure 1; A sample trace visualizing the effect of MRB in cumulative concentration on isolated ureteral strips. Molar concentrations are depicted in means of logarithmic value). The decrease in frequency was statistically significant in presence of MRB at 10^-6.5 - 10^-4.5 M (Figure 2;  Response values were proportioned with baseline contraction. All data in graphs is presented as arithmetic mean ± standard error of the mean. a p<0.05, b p<0.005). Also, the decrease in spontaneous contraction frequency in terms of percentage change was statistically significant at 10^-8 - 10^-4.5 M. The MRB lowered the spontaneous ureteric contractile force in a dose-dependent manner compared to the baseline contractile force. The decrease in amplitudes was statistically significant at 10^-7 - 10^-4.5 M concentrations.

Conclusion

The Mirabegron shows suppressive properties on the human ureter activity in vitro. This effect could be achieved in the dose-dependent fashion in isolated tissue strips showing spontaneous activity.

Funding

This study was financially supported by the Scientific Research Unit of Hacettepe University, Turkey.

Co-Authors

Meylis Artykov,
Department of Urology, Hacettepe University

Esin Ozcelebi,
Department of Pharmacology, Hacettepe University

Mehmet Yildirim Sara, Prof.
Department of Pharmacology, Hacettepe University

Alper Bektas Iskit, Prof.
Department of Pharmacology, Hacettepe University

Fazil Tuncay Aki, Prof.
Department of Urology, Hacettepe University