TY  - JOUR
AU  - Novaković, Radmila
AU  - Radunović, Nebojša
AU  - Marković-Lipkovski, Jasmina
AU  - Cirović, S.
AU  - Beleslin-Cokić, Bojana B.
AU  - Ilić, B.
AU  - Ivković, Branka
AU  - Heinle, Helmut
AU  - Živanović, Vladimir
AU  - Gojković-Bukarica, Ljiljana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2462
AB  - The ideal agent for prevention and treatment of uterine abnormal contractility has not been found. The polyphenol resveratrol possesses a wide spectrum of pharmacologic properties, but its influence on the contractility of human myometrium is not defined. The present study evaluated the effect of resveratrol on the oxytocin-induced contractions of human term pregnant myometrium in vitro and the contribution of different K+ channels to resveratrol action. Resveratrol induced a concentration-dependent relaxation of myometrium contractions (pD(2) value and maximal responses were 4.52 and 82.25%, respectively). Glibenclamide, a selective blocker of ATP-sensitive (K-ATP), iberiotoxin, a selective blockers of big-calcium sensitive (BKCa) and 4-aminopiridine, a non-selective blocker of voltage-sensitive (Kv) channels induced a significant shift to the right of the concentration-response curves of resveratrol. Inhibition achieved by 0.1 mM resveratrol was insensitive to all K+ channel blockers. A K+ channel opener, pinacidil, inhibited oxytocin-induced contractions of pregnant myometrium with comparable potency and efficacy to resveratrol (pD(2) values and maximal relaxation were 4.52 and 83.67%, respectively). Based on K+ channel opener/blocker affinities, it appears that the inhibitory response of resveratrol involves different myometrial K+ channels. When applied in high concentrations, resveratrol has an additional K+-channel-independent mechanism(s) of action. Furthermore, immunohistochemistry staining and western blot analyses detected the presence and distribution of K-ATP, BKCa and Kv channel proteins in pregnant myometrium.
PB  - Oxford Univ Press, Oxford
T2  - Molecular Human Reproduction
T1  - Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium
VL  - 21
IS  - 6
SP  - 545
EP  - 551
DO  - 10.1093/molehr/gav011
ER  - 

@article{
author = "Novaković, Radmila and Radunović, Nebojša and Marković-Lipkovski, Jasmina and Cirović, S. and Beleslin-Cokić, Bojana B. and Ilić, B. and Ivković, Branka and Heinle, Helmut and Živanović, Vladimir and Gojković-Bukarica, Ljiljana",
year = "2015",
abstract = "The ideal agent for prevention and treatment of uterine abnormal contractility has not been found. The polyphenol resveratrol possesses a wide spectrum of pharmacologic properties, but its influence on the contractility of human myometrium is not defined. The present study evaluated the effect of resveratrol on the oxytocin-induced contractions of human term pregnant myometrium in vitro and the contribution of different K+ channels to resveratrol action. Resveratrol induced a concentration-dependent relaxation of myometrium contractions (pD(2) value and maximal responses were 4.52 and 82.25%, respectively). Glibenclamide, a selective blocker of ATP-sensitive (K-ATP), iberiotoxin, a selective blockers of big-calcium sensitive (BKCa) and 4-aminopiridine, a non-selective blocker of voltage-sensitive (Kv) channels induced a significant shift to the right of the concentration-response curves of resveratrol. Inhibition achieved by 0.1 mM resveratrol was insensitive to all K+ channel blockers. A K+ channel opener, pinacidil, inhibited oxytocin-induced contractions of pregnant myometrium with comparable potency and efficacy to resveratrol (pD(2) values and maximal relaxation were 4.52 and 83.67%, respectively). Based on K+ channel opener/blocker affinities, it appears that the inhibitory response of resveratrol involves different myometrial K+ channels. When applied in high concentrations, resveratrol has an additional K+-channel-independent mechanism(s) of action. Furthermore, immunohistochemistry staining and western blot analyses detected the presence and distribution of K-ATP, BKCa and Kv channel proteins in pregnant myometrium.",
publisher = "Oxford Univ Press, Oxford",
journal = "Molecular Human Reproduction",
title = "Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium",
volume = "21",
number = "6",
pages = "545-551",
doi = "10.1093/molehr/gav011"
}

Novaković, R., Radunović, N., Marković-Lipkovski, J., Cirović, S., Beleslin-Cokić, B. B., Ilić, B., Ivković, B., Heinle, H., Živanović, V.,& Gojković-Bukarica, L.. (2015). Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium. in Molecular Human Reproduction
Oxford Univ Press, Oxford., 21(6), 545-551.
https://doi.org/10.1093/molehr/gav011

Novaković R, Radunović N, Marković-Lipkovski J, Cirović S, Beleslin-Cokić BB, Ilić B, Ivković B, Heinle H, Živanović V, Gojković-Bukarica L. Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium. in Molecular Human Reproduction. 2015;21(6):545-551.
doi:10.1093/molehr/gav011 .

Novaković, Radmila, Radunović, Nebojša, Marković-Lipkovski, Jasmina, Cirović, S., Beleslin-Cokić, Bojana B., Ilić, B., Ivković, Branka, Heinle, Helmut, Živanović, Vladimir, Gojković-Bukarica, Ljiljana, "Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium" in Molecular Human Reproduction, 21, no. 6 (2015):545-551,
https://doi.org/10.1093/molehr/gav011 . .

TY  - JOUR
AU  - Ivković, Branka
AU  - Vladimirov, Sote
AU  - Novaković, Radmila
AU  - Ćupić, Vitomir
AU  - Heinle, Helmut
AU  - Gojković-Bukarica, Ljiljana
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1740
AB  - Our aim was to define how different chemical properties of newly developed phenylpropiophenone derivates (PhPds) influenced their potency and efficacy to relax rat aorta. A contribution of ion channels in the PhPds and propafenone mechanism of vasodilatation was tested. PhPds were syntethysed by substitution in the benzyl moiety with -F, -CH3 or -CF3 groups on the ortho or para position. The vasodilatation by PhPds was examined on the rings of rat aorta precontracted with phenylephrine. In order to test involvement of voltage-gated Na+ and K+ channels and L-type Ca2+ channels in a mechanism of action of PhPds, we used their blockers: lidocaine, nifedipine and 4-aminopiridine, respectively. Aorta was more sensitive to 5-ortho-trifluoromethyl derivate than to propafenone and other PhPds. The 5-para-methyl derivate had lower potency and efficacy than propafenone and other PhPds. Lidocaine did not influenced relaxation induced by PhPds, but slightly inhibited the effect of propafenone. The 4-aminopiridine only inhibited relaxation induced by 5-para-methyl derivate. Nifedipine inhibited relaxation of the rat aorta induced by 5-ortho-trifluoromethyl derivate and by propafenone. Introduction of 5-ortho-trifluoromethyl and 5-para-methyl group in the benzyl moiety of propafenone molecule changed its potency, efficacy and mechanism of action in the rat aorta. The 4-aminopiridine- and nifedipine sensitive ion channels are involved in mechanism of action of 5-para-methyl and 5-ortho-trifluoromethyl derivate. The introduction of other tested groups in the benzyl moiety does not affect pharmacological properties of the PhPds in relation to propafenone.
PB  - Georg Thieme Verlag Kg, Stuttgart
T2  - Arzneimittelforschung - Drug Research
T1  - The Novel Phenylpropiophenone Derivates Induced Relaxation of Isolated Rat Aorta
VL  - 62
IS  - 7
SP  - 345
EP  - 350
DO  - 10.1055/s-0032-1312617
ER  - 

@article{
author = "Ivković, Branka and Vladimirov, Sote and Novaković, Radmila and Ćupić, Vitomir and Heinle, Helmut and Gojković-Bukarica, Ljiljana",
year = "2012",
abstract = "Our aim was to define how different chemical properties of newly developed phenylpropiophenone derivates (PhPds) influenced their potency and efficacy to relax rat aorta. A contribution of ion channels in the PhPds and propafenone mechanism of vasodilatation was tested. PhPds were syntethysed by substitution in the benzyl moiety with -F, -CH3 or -CF3 groups on the ortho or para position. The vasodilatation by PhPds was examined on the rings of rat aorta precontracted with phenylephrine. In order to test involvement of voltage-gated Na+ and K+ channels and L-type Ca2+ channels in a mechanism of action of PhPds, we used their blockers: lidocaine, nifedipine and 4-aminopiridine, respectively. Aorta was more sensitive to 5-ortho-trifluoromethyl derivate than to propafenone and other PhPds. The 5-para-methyl derivate had lower potency and efficacy than propafenone and other PhPds. Lidocaine did not influenced relaxation induced by PhPds, but slightly inhibited the effect of propafenone. The 4-aminopiridine only inhibited relaxation induced by 5-para-methyl derivate. Nifedipine inhibited relaxation of the rat aorta induced by 5-ortho-trifluoromethyl derivate and by propafenone. Introduction of 5-ortho-trifluoromethyl and 5-para-methyl group in the benzyl moiety of propafenone molecule changed its potency, efficacy and mechanism of action in the rat aorta. The 4-aminopiridine- and nifedipine sensitive ion channels are involved in mechanism of action of 5-para-methyl and 5-ortho-trifluoromethyl derivate. The introduction of other tested groups in the benzyl moiety does not affect pharmacological properties of the PhPds in relation to propafenone.",
publisher = "Georg Thieme Verlag Kg, Stuttgart",
journal = "Arzneimittelforschung - Drug Research",
title = "The Novel Phenylpropiophenone Derivates Induced Relaxation of Isolated Rat Aorta",
volume = "62",
number = "7",
pages = "345-350",
doi = "10.1055/s-0032-1312617"
}

Ivković, B., Vladimirov, S., Novaković, R., Ćupić, V., Heinle, H.,& Gojković-Bukarica, L.. (2012). The Novel Phenylpropiophenone Derivates Induced Relaxation of Isolated Rat Aorta. in Arzneimittelforschung - Drug Research
Georg Thieme Verlag Kg, Stuttgart., 62(7), 345-350.
https://doi.org/10.1055/s-0032-1312617

Ivković B, Vladimirov S, Novaković R, Ćupić V, Heinle H, Gojković-Bukarica L. The Novel Phenylpropiophenone Derivates Induced Relaxation of Isolated Rat Aorta. in Arzneimittelforschung - Drug Research. 2012;62(7):345-350.
doi:10.1055/s-0032-1312617 .

Ivković, Branka, Vladimirov, Sote, Novaković, Radmila, Ćupić, Vitomir, Heinle, Helmut, Gojković-Bukarica, Ljiljana, "The Novel Phenylpropiophenone Derivates Induced Relaxation of Isolated Rat Aorta" in Arzneimittelforschung - Drug Research, 62, no. 7 (2012):345-350,
https://doi.org/10.1055/s-0032-1312617 . .

TY  - JOUR
AU  - Gojković-Bukarica, Ljiljana
AU  - Beleslin-Cokić, Bojana B.
AU  - Novaković, Aleksandra
AU  - Perić, Miodrag
AU  - Marković-Lipkovski, Jasmina
AU  - Cirović, Sanja Z.
AU  - Nezić, Dušan
AU  - Lesić, Aleksandar R.
AU  - Kanjuh, Vladimir
AU  - Heinle, Helmut
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1571
AB  - Because adrenergic contractions can contribute to the development of life-threatening spasm of coronary artery bypass graft, this study was performed to investigate the effect of adenosine 3-phosphate (ATP)-sensitive K(+) channel (K(ATP)) opener P1075 on contractions of isolated human saphenous vein (HSV) and human internal mammary artery (HIMA). Phasic contractions were evoked by electric field stimulation (20 Hz) and noradrenaline. The sustained contractions were evoked by phenylephrine. The presence of pore-forming Kir6.1 and Kir6.2 subunits of the K(ATP) channels in the HIMA and only Kir6.2 in the HSV was confirmed immunomorphologically. P1075 inhibited in the HSV only, the electrical field stimulation contractions more strongly than noradrenaline contractions. In addition, the phenylephrine contractions of HSV were more sensitive to P1075 in comparison to those of HIMA. Glibenclamide, a K(ATP) channel blocker antagonized the vasodilatation produced by P1075 in both grafts differently, because its effect was more prominent on the P1075-induced inhibition of contractions of HSV than of HIMA. We conclude that P1075 has a vasorelaxant effect and inhibited adrenergic contractions of the tested grafts. This effect is graft and vasoconstrictor selective and seems to be mediated by Kir6.1-and/or Kir6.2-containing K(ATP) channels. Thus, P1075 can be considered as a potential drug in the prevention of graft spasm.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Journal of Cardiovascular Pharmacology
T1  - The Effects of Potassium Channel Opener P1075 on the Human Saphenous Vein and Human Internal Mammary Artery
VL  - 57
IS  - 6
SP  - 648
EP  - 655
DO  - 10.1097/FJC.0b013e3182145850
ER  - 

@article{
author = "Gojković-Bukarica, Ljiljana and Beleslin-Cokić, Bojana B. and Novaković, Aleksandra and Perić, Miodrag and Marković-Lipkovski, Jasmina and Cirović, Sanja Z. and Nezić, Dušan and Lesić, Aleksandar R. and Kanjuh, Vladimir and Heinle, Helmut",
year = "2011",
abstract = "Because adrenergic contractions can contribute to the development of life-threatening spasm of coronary artery bypass graft, this study was performed to investigate the effect of adenosine 3-phosphate (ATP)-sensitive K(+) channel (K(ATP)) opener P1075 on contractions of isolated human saphenous vein (HSV) and human internal mammary artery (HIMA). Phasic contractions were evoked by electric field stimulation (20 Hz) and noradrenaline. The sustained contractions were evoked by phenylephrine. The presence of pore-forming Kir6.1 and Kir6.2 subunits of the K(ATP) channels in the HIMA and only Kir6.2 in the HSV was confirmed immunomorphologically. P1075 inhibited in the HSV only, the electrical field stimulation contractions more strongly than noradrenaline contractions. In addition, the phenylephrine contractions of HSV were more sensitive to P1075 in comparison to those of HIMA. Glibenclamide, a K(ATP) channel blocker antagonized the vasodilatation produced by P1075 in both grafts differently, because its effect was more prominent on the P1075-induced inhibition of contractions of HSV than of HIMA. We conclude that P1075 has a vasorelaxant effect and inhibited adrenergic contractions of the tested grafts. This effect is graft and vasoconstrictor selective and seems to be mediated by Kir6.1-and/or Kir6.2-containing K(ATP) channels. Thus, P1075 can be considered as a potential drug in the prevention of graft spasm.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Journal of Cardiovascular Pharmacology",
title = "The Effects of Potassium Channel Opener P1075 on the Human Saphenous Vein and Human Internal Mammary Artery",
volume = "57",
number = "6",
pages = "648-655",
doi = "10.1097/FJC.0b013e3182145850"
}

Gojković-Bukarica, L., Beleslin-Cokić, B. B., Novaković, A., Perić, M., Marković-Lipkovski, J., Cirović, S. Z., Nezić, D., Lesić, A. R., Kanjuh, V.,& Heinle, H.. (2011). The Effects of Potassium Channel Opener P1075 on the Human Saphenous Vein and Human Internal Mammary Artery. in Journal of Cardiovascular Pharmacology
Lippincott Williams & Wilkins, Philadelphia., 57(6), 648-655.
https://doi.org/10.1097/FJC.0b013e3182145850

Gojković-Bukarica L, Beleslin-Cokić BB, Novaković A, Perić M, Marković-Lipkovski J, Cirović SZ, Nezić D, Lesić AR, Kanjuh V, Heinle H. The Effects of Potassium Channel Opener P1075 on the Human Saphenous Vein and Human Internal Mammary Artery. in Journal of Cardiovascular Pharmacology. 2011;57(6):648-655.
doi:10.1097/FJC.0b013e3182145850 .

Gojković-Bukarica, Ljiljana, Beleslin-Cokić, Bojana B., Novaković, Aleksandra, Perić, Miodrag, Marković-Lipkovski, Jasmina, Cirović, Sanja Z., Nezić, Dušan, Lesić, Aleksandar R., Kanjuh, Vladimir, Heinle, Helmut, "The Effects of Potassium Channel Opener P1075 on the Human Saphenous Vein and Human Internal Mammary Artery" in Journal of Cardiovascular Pharmacology, 57, no. 6 (2011):648-655,
https://doi.org/10.1097/FJC.0b013e3182145850 . .

TY  - JOUR
AU  - Gojković-Bukarica, Ljiljana
AU  - Novaković, Aleksandra
AU  - Kanjuh, Vladimir
AU  - Bumbasirević, Marko
AU  - Lesić, Aleksandar
AU  - Heinle, Helmut
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1041
AB  - Recently it has been suggested that resveratrol relaxes different isolated arteries. The present study addressed the question whether different ion channels are involved in the endothelium-independent mechanism of vasodilatation induced by resveratrol. For that purpose, we tested the action of resveratrol on the rat mesenteric artery without endothelium. Resveratrol induced con centration-dependent relaxation of rat mesenteric artery. Among the K+-channel blockers, 4-amynopiridine (4-AP) moderately antagonized the resveratrol-induced relaxation, while glibendamide, tetraethylammonium chloride, charybdotoxin, margatoxin, and barium chloride did not inhibit resveratrol-induced vasorelaxation. In rings, precontracted with 100 mM K+, the relaxant responses to resveratrol were highly significantly shifted to the right compared to those obtained in rings precontracted with phenylephrine, but resveratrol-induced maximal relaxation was only slightly affected. In order to minimize the influence of K+ channels and voltage-gated Ca2+ channels (VGCCs) in vascular smooth muscle, the third contraction was made by 100 in M K- in the presence of nifedipine. The relaxant response to resveratrol was abolished. Thus, the mechanism of vasorelaxation induced by resveratrol probably involves activation of 4-AP-sensitive K+ channels. Its ability to completely relax the mesenteric artery precontracted with K+-rich solution suggests that K channel-independent mechanism(s) are involved in its vasorelaxant effect. It seems that interaction with VGCCs plays a part in this K+ channel-independent effect of resveratrol.
PB  - Japanese Pharmacological Soc, Kyoto
T2  - Journal of Pharmacological Sciences
T1  - A role of ion channels in the endothelium-independent relaxation of rat mesenteric artery induced by resveratrol
VL  - 108
IS  - 1
SP  - 124
EP  - 130
DO  - 10.1254/jphs.08128FP
ER  - 

@article{
author = "Gojković-Bukarica, Ljiljana and Novaković, Aleksandra and Kanjuh, Vladimir and Bumbasirević, Marko and Lesić, Aleksandar and Heinle, Helmut",
year = "2008",
abstract = "Recently it has been suggested that resveratrol relaxes different isolated arteries. The present study addressed the question whether different ion channels are involved in the endothelium-independent mechanism of vasodilatation induced by resveratrol. For that purpose, we tested the action of resveratrol on the rat mesenteric artery without endothelium. Resveratrol induced con centration-dependent relaxation of rat mesenteric artery. Among the K+-channel blockers, 4-amynopiridine (4-AP) moderately antagonized the resveratrol-induced relaxation, while glibendamide, tetraethylammonium chloride, charybdotoxin, margatoxin, and barium chloride did not inhibit resveratrol-induced vasorelaxation. In rings, precontracted with 100 mM K+, the relaxant responses to resveratrol were highly significantly shifted to the right compared to those obtained in rings precontracted with phenylephrine, but resveratrol-induced maximal relaxation was only slightly affected. In order to minimize the influence of K+ channels and voltage-gated Ca2+ channels (VGCCs) in vascular smooth muscle, the third contraction was made by 100 in M K- in the presence of nifedipine. The relaxant response to resveratrol was abolished. Thus, the mechanism of vasorelaxation induced by resveratrol probably involves activation of 4-AP-sensitive K+ channels. Its ability to completely relax the mesenteric artery precontracted with K+-rich solution suggests that K channel-independent mechanism(s) are involved in its vasorelaxant effect. It seems that interaction with VGCCs plays a part in this K+ channel-independent effect of resveratrol.",
publisher = "Japanese Pharmacological Soc, Kyoto",
journal = "Journal of Pharmacological Sciences",
title = "A role of ion channels in the endothelium-independent relaxation of rat mesenteric artery induced by resveratrol",
volume = "108",
number = "1",
pages = "124-130",
doi = "10.1254/jphs.08128FP"
}

Gojković-Bukarica, L., Novaković, A., Kanjuh, V., Bumbasirević, M., Lesić, A.,& Heinle, H.. (2008). A role of ion channels in the endothelium-independent relaxation of rat mesenteric artery induced by resveratrol. in Journal of Pharmacological Sciences
Japanese Pharmacological Soc, Kyoto., 108(1), 124-130.
https://doi.org/10.1254/jphs.08128FP

Gojković-Bukarica L, Novaković A, Kanjuh V, Bumbasirević M, Lesić A, Heinle H. A role of ion channels in the endothelium-independent relaxation of rat mesenteric artery induced by resveratrol. in Journal of Pharmacological Sciences. 2008;108(1):124-130.
doi:10.1254/jphs.08128FP .

Gojković-Bukarica, Ljiljana, Novaković, Aleksandra, Kanjuh, Vladimir, Bumbasirević, Marko, Lesić, Aleksandar, Heinle, Helmut, "A role of ion channels in the endothelium-independent relaxation of rat mesenteric artery induced by resveratrol" in Journal of Pharmacological Sciences, 108, no. 1 (2008):124-130,
https://doi.org/10.1254/jphs.08128FP . .