THE IMPORTANCE OF POTASSIUM CHANNELS IN THE MECHANISM OF THE RELAXING EFFECT OF PENTOXIFYLLINE ON ISOLATED RAT UTERI
University of Kragujevac, Faculty of Science
Background. Pentoxifylline is a methylxanthine derivative that is used to treat peripheral vascular disease. One of the mechanisms of action of pentoxifylline is the vasodilatation of blood vessels. Th is study examined the eff ect of increasing pentoxifylline concentrations on the contractility of isolated rat uteri in the presence of a potassium channel antagonist. Methods. Th e 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). The preload of the preparation was approximately 1 g. Th e uteri were allowed to contract spontaneously or in the presence of Ca2+ (0.018 and 0.36 mM) and acetylcholine (ACh) and were treated with pentoxifylline. Results. Pentoxifylline caused concentration-dependent inhibition of spontaneous rhythmic uterine activity and uterine activity caused by calcium Ca2+ (0.018 mM and 0,36 mM). We showed that the inhibitory eff ects of pentoxifylline depend on the type of muscle contractions activated and that the inhibitory eff ect is signifi cantly stronger for spontaneous rhythmic activity and forin Ca2 -induced contractions of isolated rat uteri+. Th e relaxing eff ect of pentoxifylline depends on the calcium concentration in the medium. Pentoxifylline exerted the weakest relaxant eff ects on contractions induced by acetylcholine. In contrast to methylene blue, tetraethylammonium, or 4-aminopyridine, glibenclamide did not antagonise the relaxing eff ect of pentoxifylline on isolated rat uteri.. Conclusion. Th e results obtained suggest that the mechanism of action of pentoxifylline does not lead to the opening of KATP channels. However, the opening of BKCa and voltage-dependent Ca2+ channels had some role, but to varying degrees, in the mechanism of the relaxing eff ect of pentoxifylline on the spontaneous rhythmic activity and calcium-induced tractions of isolated rat uteri. Our results provide additional confi rmation of the dominance of the NO/cGMP signalling pathway in the mechanism of the relaxing eff ect of pentoxifylline (because the presence of methylene blue signifi cantly antagonised this eff ect) in relation to the opening of potassium channels, especially KATP channels. Th ese results indicate that pentoxifylline could be a potential tocolytic drug.
pentoxifylline, rat uterus, potassium channel blockers, glibenclamide (GLB), tetraethylammonium (TEA), 4-aminopyridine (4-A ), methylene blue (MB)