Прегледај по Аутор "Milovanovic, Slobodan R."

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    INFLUENCE OF MODULATORS OF RELAXANT EFFECT OF PENTOXYPHYLLINE IN ISOLATED RAT UTERUS
    (University of Kragujevac, Faculty of Science, 2010) Kordic-Bojinovic, Jelena; Jokanovic, Dragana; Stankovic, Dragana; Jankovic, Slobodan; Milovanovic, Slobodan R.
    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.
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    THE IMPORTANCE OF POTASSIUM CHANNELS IN THE MECHANISM OF THE RELAXING EFFECT OF PENTOXIFYLLINE ON ISOLATED RAT UTERI
    (University of Kragujevac, Faculty of Science, 2013) Milovanovic, Slobodan R.; Kordic-Bojinovic, Jelena; Djordjevic, Stevanka; Drakul, Dragana; Sokolovic, Dragana; Miletic, Natasa; Blagojevic, Dusko
    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.