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  - 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  - CONF
AU  - Gojković-Bukarica, Ljiljana
AU  - Novaković, Aleksandra
AU  - Beleslin-Cokić, Bojana B.
AU  - Marković-Lipkovski, Jasmina
AU  - Perić, M.
AU  - Nezić, D.
AU  - Kanjuh, Vladimir
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1390
PB  - Wiley-Blackwell Publishing, Inc, Malden
C3  - European Journal of Clinical Investigation
T1  - The effect of P1075 on the isolated human saphenous vein
VL  - 40
IS  - Suppl. 1
SP  - 5
EP  - 5
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1390
ER  - 

@conference{
author = "Gojković-Bukarica, Ljiljana and Novaković, Aleksandra and Beleslin-Cokić, Bojana B. and Marković-Lipkovski, Jasmina and Perić, M. and Nezić, D. and Kanjuh, Vladimir",
year = "2010",
publisher = "Wiley-Blackwell Publishing, Inc, Malden",
journal = "European Journal of Clinical Investigation",
title = "The effect of P1075 on the isolated human saphenous vein",
volume = "40",
number = "Suppl. 1",
pages = "5-5",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1390"
}

Gojković-Bukarica, L., Novaković, A., Beleslin-Cokić, B. B., Marković-Lipkovski, J., Perić, M., Nezić, D.,& Kanjuh, V.. (2010). The effect of P1075 on the isolated human saphenous vein. in European Journal of Clinical Investigation
Wiley-Blackwell Publishing, Inc, Malden., 40(Suppl. 1), 5-5.
https://hdl.handle.net/21.15107/rcub_farfar_1390

Gojković-Bukarica L, Novaković A, Beleslin-Cokić BB, Marković-Lipkovski J, Perić M, Nezić D, Kanjuh V. The effect of P1075 on the isolated human saphenous vein. in European Journal of Clinical Investigation. 2010;40(Suppl. 1):5-5.
https://hdl.handle.net/21.15107/rcub_farfar_1390 .

Gojković-Bukarica, Ljiljana, Novaković, Aleksandra, Beleslin-Cokić, Bojana B., Marković-Lipkovski, Jasmina, Perić, M., Nezić, D., Kanjuh, Vladimir, "The effect of P1075 on the isolated human saphenous vein" in European Journal of Clinical Investigation, 40, no. Suppl. 1 (2010):5-5,
https://hdl.handle.net/21.15107/rcub_farfar_1390 .

TY  - JOUR
AU  - Novaković, Aleksandra
AU  - Gojković-Bukarica, Ljiljana
AU  - Perić, M.
AU  - Nežić, D.
AU  - Đukanović, B.
AU  - Lešić, A.
AU  - Bumbaširević, M.
AU  - Marković-Lipkovski, Jasmina
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/871
AB  - Resveratrol, a polyphenol present in wine, has been thought to be responsible for cardiovascular benefits associated with moderate wine consumption. It is also present in the plant Polygonum Cuspidatum. The mechanism of cardiovascular benefits probably includes vasorelaxation, antioxidant and anti-platelet effects of resveratrol. The mechanisms by which resveratrol causes vasodilatation are uncertain. The aim of this study was to investigate the mechanism(s) of resveratrol induced vasorelaxation in human internal mammary artery (HIMA) with endothelium. HIMA rings were precontracted by phenylephrine. Resveratrol induced relaxation of the HIMA rings with endothelium. LNAME, an inhibitor of NO synthase, and methylene blue, an inhibitor of guanylate cyclase, abolished relaxation of HIMA induced by resveratrol. Highly selective blocker of ATP-sensitive K channels, glibenclamide as well as a nonselective blocker of big Ca-sensitive K+ channels, charybdotoxin did not block resveratrol-induced relaxation of HIMA. 4-Aminopyridine and margatoxin, blockers of voltage-gated K+ (KV) channels, abolished endothelium-dependent relaxation of HIMA, induced by resveratrol. In conclusion, we have shown that resveratrol induces relaxation of HIMA with endothelium. It seems that NO and smooth muscle KV channels are included in this relaxation.
AB  - Smatra se da rezveratrol kao jedna polifenolna komponenta prisutna u značajnim količinama u crnom vinu, smanjuje rizik od razvoja ateroskleroze i koronarne bolesti. U mehanizam kardioprotektivnog delovanja verovatno su uključ eni antioksidativno, antitrombocitno i vazodilatatorno delovanje rezveratrola. Mehanizam vazodilatacije još uvek nije poznat, pa je cilj ovog rada bio da se ispitaju efekti i mehanizam vazorelaksantnog delovanja rezveratrola na humanoj unutraš njoj torakalnoj arteriji sa endotelom. Unutrašnja torakalna arterija je prekontrahovana fenilefrinom. Rezveratrol je koncentracijski-zavisno relaksirao unutrašnju torakalnu arteriju čoveka. L-NAME, inhibitor NO sintaze, i metilensko plavo, inhibitor solubilne gvanilat ciklaze, su antagonizovali relaksaciju unutrašnje torakalne arterije sa intaktnim endotelom, prouzrokovanu rezveratrolom. Visoko selektivni blokator ATP-senzitivnih K+ kanala, glibenklamid, kao i neselektivni blokator velikih Ca-senzitivnih K+ kanala, karibdotoksin nisu antagonizovali rezveratrolom indukovanu relaksaciju unutrašnje torakalne arterije. 4-Aminopiridin i margatoksin, blokatori voltažnih K+ kanala su antagonizovali relaksaciju prouzrokovanu rezveratrolom. Na osnovu ovih činjenica se može zaključiti da je endotel-zavisna relaksacija unutrašnje torakalne arterije čoveka, prouzrokovana rezveratrolom, verovatno posredovana NO. Izgleda, da su 4-aminopiriin- i margatoksin-senzitivni K-kanali smešteni u membrani vaskularnih glatko-mišićnih ćelija humane unutrašnje torakalne arterije, uključeni u mehanizam endotel-zavisne relaksacije prouzrokovane rezveratrolom.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta veterinaria
T1  - Endothelium-dependent relaxation of internal mammary artery produced by resveratrol
T1  - Endotel-zavisna relaksacija unutrašnje torakalne arterije prouzrokovana rezveratrolom
VL  - 56
IS  - 2-3
SP  - 203
EP  - 213
DO  - 10.2298/AVB0603203N
ER  - 

@article{
author = "Novaković, Aleksandra and Gojković-Bukarica, Ljiljana and Perić, M. and Nežić, D. and Đukanović, B. and Lešić, A. and Bumbaširević, M. and Marković-Lipkovski, Jasmina",
year = "2006",
abstract = "Resveratrol, a polyphenol present in wine, has been thought to be responsible for cardiovascular benefits associated with moderate wine consumption. It is also present in the plant Polygonum Cuspidatum. The mechanism of cardiovascular benefits probably includes vasorelaxation, antioxidant and anti-platelet effects of resveratrol. The mechanisms by which resveratrol causes vasodilatation are uncertain. The aim of this study was to investigate the mechanism(s) of resveratrol induced vasorelaxation in human internal mammary artery (HIMA) with endothelium. HIMA rings were precontracted by phenylephrine. Resveratrol induced relaxation of the HIMA rings with endothelium. LNAME, an inhibitor of NO synthase, and methylene blue, an inhibitor of guanylate cyclase, abolished relaxation of HIMA induced by resveratrol. Highly selective blocker of ATP-sensitive K channels, glibenclamide as well as a nonselective blocker of big Ca-sensitive K+ channels, charybdotoxin did not block resveratrol-induced relaxation of HIMA. 4-Aminopyridine and margatoxin, blockers of voltage-gated K+ (KV) channels, abolished endothelium-dependent relaxation of HIMA, induced by resveratrol. In conclusion, we have shown that resveratrol induces relaxation of HIMA with endothelium. It seems that NO and smooth muscle KV channels are included in this relaxation., Smatra se da rezveratrol kao jedna polifenolna komponenta prisutna u značajnim količinama u crnom vinu, smanjuje rizik od razvoja ateroskleroze i koronarne bolesti. U mehanizam kardioprotektivnog delovanja verovatno su uključ eni antioksidativno, antitrombocitno i vazodilatatorno delovanje rezveratrola. Mehanizam vazodilatacije još uvek nije poznat, pa je cilj ovog rada bio da se ispitaju efekti i mehanizam vazorelaksantnog delovanja rezveratrola na humanoj unutraš njoj torakalnoj arteriji sa endotelom. Unutrašnja torakalna arterija je prekontrahovana fenilefrinom. Rezveratrol je koncentracijski-zavisno relaksirao unutrašnju torakalnu arteriju čoveka. L-NAME, inhibitor NO sintaze, i metilensko plavo, inhibitor solubilne gvanilat ciklaze, su antagonizovali relaksaciju unutrašnje torakalne arterije sa intaktnim endotelom, prouzrokovanu rezveratrolom. Visoko selektivni blokator ATP-senzitivnih K+ kanala, glibenklamid, kao i neselektivni blokator velikih Ca-senzitivnih K+ kanala, karibdotoksin nisu antagonizovali rezveratrolom indukovanu relaksaciju unutrašnje torakalne arterije. 4-Aminopiridin i margatoksin, blokatori voltažnih K+ kanala su antagonizovali relaksaciju prouzrokovanu rezveratrolom. Na osnovu ovih činjenica se može zaključiti da je endotel-zavisna relaksacija unutrašnje torakalne arterije čoveka, prouzrokovana rezveratrolom, verovatno posredovana NO. Izgleda, da su 4-aminopiriin- i margatoksin-senzitivni K-kanali smešteni u membrani vaskularnih glatko-mišićnih ćelija humane unutrašnje torakalne arterije, uključeni u mehanizam endotel-zavisne relaksacije prouzrokovane rezveratrolom.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta veterinaria",
title = "Endothelium-dependent relaxation of internal mammary artery produced by resveratrol, Endotel-zavisna relaksacija unutrašnje torakalne arterije prouzrokovana rezveratrolom",
volume = "56",
number = "2-3",
pages = "203-213",
doi = "10.2298/AVB0603203N"
}

Novaković, A., Gojković-Bukarica, L., Perić, M., Nežić, D., Đukanović, B., Lešić, A., Bumbaširević, M.,& Marković-Lipkovski, J.. (2006). Endothelium-dependent relaxation of internal mammary artery produced by resveratrol. in Acta veterinaria
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 56(2-3), 203-213.
https://doi.org/10.2298/AVB0603203N

Novaković A, Gojković-Bukarica L, Perić M, Nežić D, Đukanović B, Lešić A, Bumbaširević M, Marković-Lipkovski J. Endothelium-dependent relaxation of internal mammary artery produced by resveratrol. in Acta veterinaria. 2006;56(2-3):203-213.
doi:10.2298/AVB0603203N .

Novaković, Aleksandra, Gojković-Bukarica, Ljiljana, Perić, M., Nežić, D., Đukanović, B., Lešić, A., Bumbaširević, M., Marković-Lipkovski, Jasmina, "Endothelium-dependent relaxation of internal mammary artery produced by resveratrol" in Acta veterinaria, 56, no. 2-3 (2006):203-213,
https://doi.org/10.2298/AVB0603203N . .