Influence of modulators of relaxant effect of pentoxyphylline in isolated rat uterus

Background. Pentoxyphylline is a methylxanthine derivative used in the treatment of peripheral vascular diseases. One eff ect of pentoxyphylline action is the vasodilatation of blood vessels. In this study, the eff ect of increasing concentrations of pentoxyphylline on contractility of isolated rat uteri was examined. Methods. Uteri were isolated from virgin Wistar rats (180–220 g) and suspended in an isolated organ bath chamber containing De Jalon’s solution and aerated with 95% O2 and 5% CO2. Th e temperature was maintained at 37oC. Isometric contractions were recorded using an isometric force transducer (Ugo Basile). Th e preload of the preparation was about 1 g. Uteri were allowed to contract spontaneously or in the presence of Ca2+ (6 mM) and were treated with pentoxyphylline. Results. Pentoxyphylline caused concentration-dependent inhibition of spontaneous rhythmic uterine activity and uterine activity induced by calcium. We showed that the inhibitory eff ect of pentoxyphylline depends on the type of muscle contraction activation, and that it is signifi cantly stronger in spontaneous contractions induced by calcium Ca2+. As opposed to methylene blue, L-arginine and glibenclamide did not antagonise the relaxing eff ect of pentoxyphylline on the isolated rat uterus. Conclusion. Our results suggest that the signaling pathway by which pentoxyphylline causes relaxation of uterine muscle cells does not involve NO because the presence of Larginine did not aff ect the action of the drug; however, it may depend on an NO-independent cGMP signaling pathway because the presence of methylene blue signifi cantly antagonised the eff ect of pentoxyphylline. Th ese results indicate that pentoxyphylline could be a potential tocolytic drug.