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PDE-5-Inhibitoren

Ein neuer Therapieansatz in der Behandlung der Harnleiterkolik?

PDE5 inhibitors

A new option in the treatment of ureteral colic?

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Zusammenfassung

Hintergrund

PDE-5-Inhibitoren stellen den Goldstandard in der medikamentösen Therapie der erektilen Dysfunktion (ED) dar. Viel versprechende Ergebnisse werden auch für weitere urologische Indikationen wie der Harnleiterkolik berichtet. Ziel der vorliegenden Arbeit war es daher, die funktionellen Effekte der PDE-5-Inhibitoren Sildenafil (SIL), Vardenafil (VAR) und Tadalafil (TAD) sowohl auf die Muskelspannung als auch auf die Konzentration zyklischer Nukleotide in der glatten Muskulatur des menschlichen Harnleiters in vitro zu testen.

Material und Methoden

Die relaxierenden Eigenschaften der PDE-5-Inhibitoren wurden mit der Organbadtechnik untersucht; der cAMP- sowie cGMP-Gehalt wurde mit spezifischen Radioimmunoassays bestimmt.

Ergebnisse

Die verschiedenen PDE-5-Inhibitoren relaxierten die Muskelspannung in der Rangfolge Var>Sil>Tad. Der cGMP-Spiegel wurde lediglich von Var auf das 3,3Fache erhöht; ein signifikanter Anstieg der cAMP-Spiegel war nicht zu verzeichnen.

Schlussfolgerung

Unsere Daten unterstreichen die Bedeutung von cGMP in der Regulation der glatten Muskulatur menschlichen Harnleiters. PDE-5-Inhibitoren könnten somit bei der Behandlung einer Harnleiterkolik zum Einsatz kommen.

Abstract

Background

PDE5 inhibitors represent the gold standard in the medical therapy of erectile dysfunction (ED). Promising results have been published regarding further urological indications such as treatment of ureteral colic. The aim of the present study was to evaluate the functional effects of the PDE5 inhibitors sildenafil (SIL), vardenafil (VAR), and tadalafil (TAD) on tissue tension and cyclic nucleotide levels of human ureteral smooth muscle segments in vitro.

Methods

Relaxant responses of human ureteral smooth muscle were investigated in vitro using the organ bath technique. Cyclic nucleotides cAMP and cGMP were determined by specific radioimmunoassays.

Results

Relaxing effects of ureteral muscle tension were observed in the rank order VAR > SIL > TAD. While only VAR significantly elevated cGMP levels 3.3-fold over control, no increase for cAMP levels was observed.

Conclusions

Our data provide evidence that cGMP is involved in the control of the normal function of the smooth musculature of the human ureter. Our findings suggest the potential of using selective inhibitors of PDE isoenzymes in the treatment of ureteral colic.

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Gratzke, C., Ückert, S., Reich, O. et al. PDE-5-Inhibitoren. Urologe 46, 1219–1223 (2007). https://doi.org/10.1007/s00120-007-1409-3

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  • DOI: https://doi.org/10.1007/s00120-007-1409-3

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