TY  - JOUR
AU  - Ivković, Branka
AU  - Gojković-Bukarica, Ljiljana
AU  - Vladimirov, S.
AU  - Novaković, Radmila
AU  - Ćupić, Vitomir
AU  - Lešić, A.
AU  - Bumbaširević, M.
AU  - Šćepanović, Radisav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2063
AB  - The information on the inhibitory effect of propafenone in vascular smooth muscle is sparse. Propafenone acts through blockage of voltage-dependent cardiac Na+ channels, L-type Ca2+ channels, voltage-sensitive K+ (Kv) channels, as well as β-adrenergic receptors in the heart. The introduction of different chemical groups in the benzyl moiety of propafenone influences pharmacological properties of newly developed derivate of propafenone. Here we investigated the effect of new ortho-chloro derivate of propafenone (5OCl) on the vascular tone of precontracted rat aorta. 5OCl produced endothelium-independent relaxation of rat aorta. In order to test the involvement of different ion channels in 5OCl mechanism of action, antagonist of Na+, lidocaine, KV channels, 4-aminopyiridine (4-AP) and L-type Ca2+ channels, nifedipine were used. All tested antagonists of ion channels did not influence the relaxation of rat aorta induced by high a concentration of 5OCl (≥10 μM), but antagonized the relaxation induced by low concentrations of this propafenone derivate. Thus, 5OCl derivate has comparable potency and efficacy as propafenone. According to its interaction with lidocaine, 4-AP and nifedipine it seems that 5OCl partly shares the mechanism of action with propafenone. The mechanism of vasodilatation induced by high micromolar concentration of 5OCl is not defined and further investigations are necessary.
AB  - Informacije o efektima propafenona na vaskularne glatke mišiće su oskudne. Propafenon blokira voltažno-zavisne Na+ kanale, Ca2+ kanale L-tipa, voltažno-senzitivne K+ (Kv) kanale i β-adrenergičke receptore u srcu. Uvođenje različitih hemijskih grupa u benzilni deo molekula propafenona utiče na promenu njegovih farmakoloških osobina. U ovoj studiji je ispitivan uticaj novog orto-hloro derivata (5OCl) propafenona na vaskularni tonus prekontrahovane aorte pacova. Orto hlorni derivat (5OCl) je izazvao endotel-nezavisnu relaksaciju aortnih prstenova. Da bi se ispitala uloga različitih jonskih kanala u ovoj relaksaciji, korišćeni su lidokain, (antagonist Na+ kanala), 4-aminopiridin (antagonist Kv kanala) i nifedipin (antagonist Ca2+ kanala L-tipa). Testirani antagonisti jonskih kanala nisu uticali na relaksaciju aorte pacova izazvanu visokom koncentracijom 5OCl (≥10 μM), ali su zato antagonizovali relaksaciju aorte koncentracijama 5OCl koje su bile manje od 10 μM. Prema tome, 5OCl derivat ima sličnu jačinu i efikasnost kao propafenon. Prema njegovoj interakciji sa lidokainom, 4-AP i nifedipinom može se reći da je mehanizam dejstva 5OCl sličan propafenonu. Mehanizam vazodilatacije 5OCl derivata u koncentracijama većim od 10 μM nije definisan i za to su potrebna dalja istraživanja.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta veterinaria
T1  - The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta
T1  - Relaksacija aorte pacova indukovana novosintetisanim orto-hlornim derivatom propafenona
VL  - 63
IS  - 4
SP  - 363
EP  - 371
DO  - 10.2298/AVB1304363I
ER  - 

@article{
author = "Ivković, Branka and Gojković-Bukarica, Ljiljana and Vladimirov, S. and Novaković, Radmila and Ćupić, Vitomir and Lešić, A. and Bumbaširević, M. and Šćepanović, Radisav",
year = "2013",
abstract = "The information on the inhibitory effect of propafenone in vascular smooth muscle is sparse. Propafenone acts through blockage of voltage-dependent cardiac Na+ channels, L-type Ca2+ channels, voltage-sensitive K+ (Kv) channels, as well as β-adrenergic receptors in the heart. The introduction of different chemical groups in the benzyl moiety of propafenone influences pharmacological properties of newly developed derivate of propafenone. Here we investigated the effect of new ortho-chloro derivate of propafenone (5OCl) on the vascular tone of precontracted rat aorta. 5OCl produced endothelium-independent relaxation of rat aorta. In order to test the involvement of different ion channels in 5OCl mechanism of action, antagonist of Na+, lidocaine, KV channels, 4-aminopyiridine (4-AP) and L-type Ca2+ channels, nifedipine were used. All tested antagonists of ion channels did not influence the relaxation of rat aorta induced by high a concentration of 5OCl (≥10 μM), but antagonized the relaxation induced by low concentrations of this propafenone derivate. Thus, 5OCl derivate has comparable potency and efficacy as propafenone. According to its interaction with lidocaine, 4-AP and nifedipine it seems that 5OCl partly shares the mechanism of action with propafenone. The mechanism of vasodilatation induced by high micromolar concentration of 5OCl is not defined and further investigations are necessary., Informacije o efektima propafenona na vaskularne glatke mišiće su oskudne. Propafenon blokira voltažno-zavisne Na+ kanale, Ca2+ kanale L-tipa, voltažno-senzitivne K+ (Kv) kanale i β-adrenergičke receptore u srcu. Uvođenje različitih hemijskih grupa u benzilni deo molekula propafenona utiče na promenu njegovih farmakoloških osobina. U ovoj studiji je ispitivan uticaj novog orto-hloro derivata (5OCl) propafenona na vaskularni tonus prekontrahovane aorte pacova. Orto hlorni derivat (5OCl) je izazvao endotel-nezavisnu relaksaciju aortnih prstenova. Da bi se ispitala uloga različitih jonskih kanala u ovoj relaksaciji, korišćeni su lidokain, (antagonist Na+ kanala), 4-aminopiridin (antagonist Kv kanala) i nifedipin (antagonist Ca2+ kanala L-tipa). Testirani antagonisti jonskih kanala nisu uticali na relaksaciju aorte pacova izazvanu visokom koncentracijom 5OCl (≥10 μM), ali su zato antagonizovali relaksaciju aorte koncentracijama 5OCl koje su bile manje od 10 μM. Prema tome, 5OCl derivat ima sličnu jačinu i efikasnost kao propafenon. Prema njegovoj interakciji sa lidokainom, 4-AP i nifedipinom može se reći da je mehanizam dejstva 5OCl sličan propafenonu. Mehanizam vazodilatacije 5OCl derivata u koncentracijama većim od 10 μM nije definisan i za to su potrebna dalja istraživanja.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta veterinaria",
title = "The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta, Relaksacija aorte pacova indukovana novosintetisanim orto-hlornim derivatom propafenona",
volume = "63",
number = "4",
pages = "363-371",
doi = "10.2298/AVB1304363I"
}

Ivković, B., Gojković-Bukarica, L., Vladimirov, S., Novaković, R., Ćupić, V., Lešić, A., Bumbaširević, M.,& Šćepanović, R.. (2013). The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta. in Acta veterinaria
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 63(4), 363-371.
https://doi.org/10.2298/AVB1304363I

Ivković B, Gojković-Bukarica L, Vladimirov S, Novaković R, Ćupić V, Lešić A, Bumbaširević M, Šćepanović R. The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta. in Acta veterinaria. 2013;63(4):363-371.
doi:10.2298/AVB1304363I .

Ivković, Branka, Gojković-Bukarica, Ljiljana, Vladimirov, S., Novaković, Radmila, Ćupić, Vitomir, Lešić, A., Bumbaširević, M., Šćepanović, Radisav, "The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta" in Acta veterinaria, 63, no. 4 (2013):363-371,
https://doi.org/10.2298/AVB1304363I . .

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 . .