TY  - CONF
AU  - Marinko, Marija
AU  - Janković, Goran
AU  - Milojević, Predrag
AU  - Stojanović, Ivan
AU  - Nenezić, Dragoslav
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
AU  - Novaković, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4492
AB  - Findings from epidemiological studies indicate that polyphenols, widespread in
human diet and with numerous biological activities, act cardioprotectively. Procyanidins are
subclass of polyphenols with high content in commonly consumed foods and beverages, such
as grapes, tea, chocolate, nuts and apples. Cardioprotective abilities of procyanidins, might, at
least partly, attribute to their vasodilator properties. Since exact mechanisms of procyanidin
B2-induced vasorelaxation are unknown, our study aimed to investigate relaxant effect of
procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms.
Discarded segments of HSV were collected from patients undergoing bypass surgery and
studied in organ baths. Procyanidin B2 caused concentration-dependent relaxation of HSV
precontracted by phenylephrine. The relaxation was strongly affected by inhibitors of
NO/cGMP pathway, L-NAME, hydroxocobalamin and ODQ. Indomethacin, a cyclooxygenase
inhibitor, significantly reduced only relaxation produced by the highest concentrations of
procyanidin B2. Combination of apamin and TRAM-34, selective blockers of small- and
intermediate-conductance Ca 2+ -activated K+ (KCa ) channels (SKCa and IK Ca ), in the presence of
L-NAME and indomethacin, did not additionally affect procyanidin B2-induced relaxation.
Additionally, relaxation induced by procyanidin B2 was partially attenuated by 4-
aminopyridine, predominant blocker of voltage-gated K+ (KV) channels, significantly
inhibited by glibenclamide, selective ATP-sensitive K+ (KATP) channels inhibitor, and almost
abolished by iberiotoxin, highly selective blocker of large-conductance KCa (BKCa ). Our results
revealed that procyanidin B2 acts as a potent vasodilator on isolated human venous graft.
Mechanism of this relaxation of HSV probably involves stimulation of NO production, as well
K+ channels opening, especially BK Ca , and partially KATP and KV
AB  - Nalazi epidemioloških studija ukazuju da polifenoli, široko rasprostranjeni u ljudskoj
ishrani i sa brojnim biološkim aktivnostima, deluju kardioprotektivno. Procijanidini su
podklasa polifenola sa visokim sadržajem u često konzumiranoj hrani i pićima, kao što su
grožđe, čaj, čokolada, orašasti plodovi i jabuke. Kardioprotektivno delovanje procijanidina
može se, bar delimično, pripisati njihovim vazodilatatornim svojstvima. S obzirom da tačni
mehanizmi pomoću kojih procijanidin B2 izaziva vazorelaksaciju nisu poznati, cilj naše
studije bio je da istražimo relaksantni efekat procijanidina B2 na izolovanoj humanoj veni
safeni (HSV) i njegove osnovne mehanizme.Neiskorišćeni segmenti HSV su uzimani od
pacijenata u toku bajpas operacija i ispitivani u kupatilu za izolovane organe. Procijanidin B2
izazvao je koncentracijski-zavisnu relaksaciju HSV prekontrahovane fenilefrinom. Na
relaksaciju su snažno uticali inhibitori NO/cGMP puta, L-NAME, hidroksokobalamin i ODQ.
Indometacin, inhibitor ciklooksigenaze, značajno je umanjio samo relaksaciju izazivanu
najvećim koncentracijama procijanidina B2. Kombinacija apamina i TRAM-34, selektivnih
blokatora Ca 2+ -zavisnih K+ (KCa ) kanala male i srednje provodljivosti (SKCa i IK Ca ), u prisustvu
L-NAME i indometacina, nije dodatno uticala na relaksaciju uzrokovanu procijanidinom B2.
Osim toga, procijanidinom B2 izazvana relaksacija bila je delimično umanjena 4-
aminopiridinom, dominantnim blokatorom voltažno-zavisnih K+ (KV) kanala, značajno
inhibirana glibenklamidom, selektivnim inhibitorom ATP-zavisnih K+ (KATP) kanala, i skoro
potpuno blokirana iberiotoksinom, selektivnim blokatorom K Ca velike provodljivosti (BK Ca).
Naši rezultati pokazuju da procijanidin B2 deluje kao moćni vazodilatator na izolovanom
humanom venskom graftu. Mehanizam ove relaksacije HSV verovatno uključuje stimulaciju
proizvodnje NO, kao i otvaranje K+ kanala, posebno BK Ca , i delimično KATP i KV
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Mechanism underlying vasorelaxation of human saphenous vein induced by procyanidin B2
T1  - Mehanizam vazorelaksacije humane vene safene izazvane procijanidinom B2
VL  - 72
IS  - 4 suplement
SP  - S190
EP  - S191
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4492
ER  - 

@conference{
author = "Marinko, Marija and Janković, Goran and Milojević, Predrag and Stojanović, Ivan and Nenezić, Dragoslav and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei and Novaković, Aleksandra",
year = "2022",
abstract = "Findings from epidemiological studies indicate that polyphenols, widespread in
human diet and with numerous biological activities, act cardioprotectively. Procyanidins are
subclass of polyphenols with high content in commonly consumed foods and beverages, such
as grapes, tea, chocolate, nuts and apples. Cardioprotective abilities of procyanidins, might, at
least partly, attribute to their vasodilator properties. Since exact mechanisms of procyanidin
B2-induced vasorelaxation are unknown, our study aimed to investigate relaxant effect of
procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms.
Discarded segments of HSV were collected from patients undergoing bypass surgery and
studied in organ baths. Procyanidin B2 caused concentration-dependent relaxation of HSV
precontracted by phenylephrine. The relaxation was strongly affected by inhibitors of
NO/cGMP pathway, L-NAME, hydroxocobalamin and ODQ. Indomethacin, a cyclooxygenase
inhibitor, significantly reduced only relaxation produced by the highest concentrations of
procyanidin B2. Combination of apamin and TRAM-34, selective blockers of small- and
intermediate-conductance Ca 2+ -activated K+ (KCa ) channels (SKCa and IK Ca ), in the presence of
L-NAME and indomethacin, did not additionally affect procyanidin B2-induced relaxation.
Additionally, relaxation induced by procyanidin B2 was partially attenuated by 4-
aminopyridine, predominant blocker of voltage-gated K+ (KV) channels, significantly
inhibited by glibenclamide, selective ATP-sensitive K+ (KATP) channels inhibitor, and almost
abolished by iberiotoxin, highly selective blocker of large-conductance KCa (BKCa ). Our results
revealed that procyanidin B2 acts as a potent vasodilator on isolated human venous graft.
Mechanism of this relaxation of HSV probably involves stimulation of NO production, as well
K+ channels opening, especially BK Ca , and partially KATP and KV, Nalazi epidemioloških studija ukazuju da polifenoli, široko rasprostranjeni u ljudskoj
ishrani i sa brojnim biološkim aktivnostima, deluju kardioprotektivno. Procijanidini su
podklasa polifenola sa visokim sadržajem u često konzumiranoj hrani i pićima, kao što su
grožđe, čaj, čokolada, orašasti plodovi i jabuke. Kardioprotektivno delovanje procijanidina
može se, bar delimično, pripisati njihovim vazodilatatornim svojstvima. S obzirom da tačni
mehanizmi pomoću kojih procijanidin B2 izaziva vazorelaksaciju nisu poznati, cilj naše
studije bio je da istražimo relaksantni efekat procijanidina B2 na izolovanoj humanoj veni
safeni (HSV) i njegove osnovne mehanizme.Neiskorišćeni segmenti HSV su uzimani od
pacijenata u toku bajpas operacija i ispitivani u kupatilu za izolovane organe. Procijanidin B2
izazvao je koncentracijski-zavisnu relaksaciju HSV prekontrahovane fenilefrinom. Na
relaksaciju su snažno uticali inhibitori NO/cGMP puta, L-NAME, hidroksokobalamin i ODQ.
Indometacin, inhibitor ciklooksigenaze, značajno je umanjio samo relaksaciju izazivanu
najvećim koncentracijama procijanidina B2. Kombinacija apamina i TRAM-34, selektivnih
blokatora Ca 2+ -zavisnih K+ (KCa ) kanala male i srednje provodljivosti (SKCa i IK Ca ), u prisustvu
L-NAME i indometacina, nije dodatno uticala na relaksaciju uzrokovanu procijanidinom B2.
Osim toga, procijanidinom B2 izazvana relaksacija bila je delimično umanjena 4-
aminopiridinom, dominantnim blokatorom voltažno-zavisnih K+ (KV) kanala, značajno
inhibirana glibenklamidom, selektivnim inhibitorom ATP-zavisnih K+ (KATP) kanala, i skoro
potpuno blokirana iberiotoksinom, selektivnim blokatorom K Ca velike provodljivosti (BK Ca).
Naši rezultati pokazuju da procijanidin B2 deluje kao moćni vazodilatator na izolovanom
humanom venskom graftu. Mehanizam ove relaksacije HSV verovatno uključuje stimulaciju
proizvodnje NO, kao i otvaranje K+ kanala, posebno BK Ca , i delimično KATP i KV",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Mechanism underlying vasorelaxation of human saphenous vein induced by procyanidin B2, Mehanizam vazorelaksacije humane vene safene izazvane procijanidinom B2",
volume = "72",
number = "4 suplement",
pages = "S190-S191",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4492"
}

Marinko, M., Janković, G., Milojević, P., Stojanović, I., Nenezić, D., Kanjuh, V., Yang, Q., He, G.,& Novaković, A.. (2022). Mechanism underlying vasorelaxation of human saphenous vein induced by procyanidin B2. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S190-S191.
https://hdl.handle.net/21.15107/rcub_farfar_4492

Marinko M, Janković G, Milojević P, Stojanović I, Nenezić D, Kanjuh V, Yang Q, He G, Novaković A. Mechanism underlying vasorelaxation of human saphenous vein induced by procyanidin B2. in Arhiv za farmaciju. 2022;72(4 suplement):S190-S191.
https://hdl.handle.net/21.15107/rcub_farfar_4492 .

Marinko, Marija, Janković, Goran, Milojević, Predrag, Stojanović, Ivan, Nenezić, Dragoslav, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, Novaković, Aleksandra, "Mechanism underlying vasorelaxation of human saphenous vein induced by procyanidin B2" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S190-S191,
https://hdl.handle.net/21.15107/rcub_farfar_4492 .

TY  - JOUR
AU  - Marinko, Marija
AU  - Hou, Hai-Tao
AU  - Stojanović, Ivan
AU  - Milojević, Predrag
AU  - Nenezić, Dragoslav
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
AU  - Novaković, Aleksandra
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3901
AB  - Hydrogen sulfide (H2S) represents the third and the youngest member of the gaseous transmitters family. The dominant effect of H2S on isolated vessels is vasodilation. As the mechanism of H2S-induced relaxation in human vessels remains unclear, the present study aimed to investigate the effects of H2S donor, sodium hydrosulfide (NaHS), on isolated human saphenous vein (HSV) and to determine the mechanism of action. Our results showed that NaHS (1 µM–3 mM) induced a concentration-dependent relaxation of endothelium-intact HSV rings pre-contracted by phenylephrine. Pre-treatment with L-NAME, ODQ and KT5823 significantly inhibited NaHS-induced relaxation, while indomethacin induced partial inhibition. Among K+ channel blockers, the combination of apamin and TRAM-34 significantly affected the relaxation produced by NaHS, while iberiotoxin and glibenclamide only reduced maximal relaxation of HSV. NaHS partially relaxed endothelium-intact rings pre-contracted by high K+, as well as phenylephrine-contracted rings in the presence of nifedipine. Additionally, the incubation of HSV rings with NaHS increased NO production. These results demonstrate that NaHS produces the concentration- and endothelium-dependent relaxation of isolated HSV. Vasorelaxation to NaHS probably involves activation of NO/cGMP/PKG pathway and partially prostacyclin. In addition, different K+ channels subtypes, especially SKCa and IKCa, as well as BKCa and KATP channels in high concentrations of NaHS, probably participate in the NaHS-induced vasorelaxation.
PB  - Blackwell Publishing Ltd
T2  - Fundamental and Clinical Pharmacology
T1  - Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein
VL  - 35
IS  - 5
SP  - 906
EP  - 918
DO  - 10.1111/fcp.12658
ER  - 

@article{
author = "Marinko, Marija and Hou, Hai-Tao and Stojanović, Ivan and Milojević, Predrag and Nenezić, Dragoslav and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei and Novaković, Aleksandra",
year = "2021",
abstract = "Hydrogen sulfide (H2S) represents the third and the youngest member of the gaseous transmitters family. The dominant effect of H2S on isolated vessels is vasodilation. As the mechanism of H2S-induced relaxation in human vessels remains unclear, the present study aimed to investigate the effects of H2S donor, sodium hydrosulfide (NaHS), on isolated human saphenous vein (HSV) and to determine the mechanism of action. Our results showed that NaHS (1 µM–3 mM) induced a concentration-dependent relaxation of endothelium-intact HSV rings pre-contracted by phenylephrine. Pre-treatment with L-NAME, ODQ and KT5823 significantly inhibited NaHS-induced relaxation, while indomethacin induced partial inhibition. Among K+ channel blockers, the combination of apamin and TRAM-34 significantly affected the relaxation produced by NaHS, while iberiotoxin and glibenclamide only reduced maximal relaxation of HSV. NaHS partially relaxed endothelium-intact rings pre-contracted by high K+, as well as phenylephrine-contracted rings in the presence of nifedipine. Additionally, the incubation of HSV rings with NaHS increased NO production. These results demonstrate that NaHS produces the concentration- and endothelium-dependent relaxation of isolated HSV. Vasorelaxation to NaHS probably involves activation of NO/cGMP/PKG pathway and partially prostacyclin. In addition, different K+ channels subtypes, especially SKCa and IKCa, as well as BKCa and KATP channels in high concentrations of NaHS, probably participate in the NaHS-induced vasorelaxation.",
publisher = "Blackwell Publishing Ltd",
journal = "Fundamental and Clinical Pharmacology",
title = "Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein",
volume = "35",
number = "5",
pages = "906-918",
doi = "10.1111/fcp.12658"
}

Marinko, M., Hou, H., Stojanović, I., Milojević, P., Nenezić, D., Kanjuh, V., Yang, Q., He, G.,& Novaković, A.. (2021). Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein. in Fundamental and Clinical Pharmacology
Blackwell Publishing Ltd., 35(5), 906-918.
https://doi.org/10.1111/fcp.12658

Marinko M, Hou H, Stojanović I, Milojević P, Nenezić D, Kanjuh V, Yang Q, He G, Novaković A. Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein. in Fundamental and Clinical Pharmacology. 2021;35(5):906-918.
doi:10.1111/fcp.12658 .

Marinko, Marija, Hou, Hai-Tao, Stojanović, Ivan, Milojević, Predrag, Nenezić, Dragoslav, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, Novaković, Aleksandra, "Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein" in Fundamental and Clinical Pharmacology, 35, no. 5 (2021):906-918,
https://doi.org/10.1111/fcp.12658 . .

TY  - JOUR
AU  - Janković, Goran
AU  - Marinko, Marija
AU  - Milojević, Predrag
AU  - Stojanović, Ivan
AU  - Nenezić, Dragoslav
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
AU  - Novaković, Aleksandra
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3515
AB  - Cardioprotective abilities of procyanidins, might, at least in part, attribute to their vasodilator properties. The present study was undertaken to assess the vasorelaxant effect of procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms. Procyanidin B2 relaxed phenylephrine-induced contraction of HSV rings in concentration-dependent manner. The relaxation was dependent on the presence of endothelium and was strongly affected by l-NAME, hydroxocobalamin or ODQ, the inhibitors of NO/cGMP pathway. Indomethacin significantly affected only the relaxation produced by the highest concentrations of procyanidin B2. Apamin and TRAM-34 combination, in the presence of l-NAME and indomethacin, did not additionally decreased procyanidin B2-induced relaxation. In the presence of K+ channel blockers, relaxation induced by procyanidin B2 was partially attenuated by 4-aminopyridine, significantly inhibited by glibenclamide and almost abolished by iberiotoxin. Procyanidin B2 also relaxed the contractions induced by phenylephrine or caffeine in Ca2+-free solution. Finally, nifedipine slightly, while thapsigargin strongly antagonized HSV relaxation. Our results indicate that procyanidin B2 induces endothelium-dependent relaxation of HSV, which results primarily from stimulation of NO production, as well K+ channels opening, especially BKCa, and partially KATP and KV. Regulation of the intracellular Ca2+ release and inhibition of Ca2+ influx probably contr
PB  - Elsevier B.V.
T2  - Journal of Pharmacological Sciences
T1  - Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft
VL  - 142
IS  - 3
SP  - 101
EP  - 108
DO  - 10.1016/j.jphs.2019.11.006
ER  - 

@article{
author = "Janković, Goran and Marinko, Marija and Milojević, Predrag and Stojanović, Ivan and Nenezić, Dragoslav and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei and Novaković, Aleksandra",
year = "2019",
abstract = "Cardioprotective abilities of procyanidins, might, at least in part, attribute to their vasodilator properties. The present study was undertaken to assess the vasorelaxant effect of procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms. Procyanidin B2 relaxed phenylephrine-induced contraction of HSV rings in concentration-dependent manner. The relaxation was dependent on the presence of endothelium and was strongly affected by l-NAME, hydroxocobalamin or ODQ, the inhibitors of NO/cGMP pathway. Indomethacin significantly affected only the relaxation produced by the highest concentrations of procyanidin B2. Apamin and TRAM-34 combination, in the presence of l-NAME and indomethacin, did not additionally decreased procyanidin B2-induced relaxation. In the presence of K+ channel blockers, relaxation induced by procyanidin B2 was partially attenuated by 4-aminopyridine, significantly inhibited by glibenclamide and almost abolished by iberiotoxin. Procyanidin B2 also relaxed the contractions induced by phenylephrine or caffeine in Ca2+-free solution. Finally, nifedipine slightly, while thapsigargin strongly antagonized HSV relaxation. Our results indicate that procyanidin B2 induces endothelium-dependent relaxation of HSV, which results primarily from stimulation of NO production, as well K+ channels opening, especially BKCa, and partially KATP and KV. Regulation of the intracellular Ca2+ release and inhibition of Ca2+ influx probably contr",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmacological Sciences",
title = "Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft",
volume = "142",
number = "3",
pages = "101-108",
doi = "10.1016/j.jphs.2019.11.006"
}

Janković, G., Marinko, M., Milojević, P., Stojanović, I., Nenezić, D., Kanjuh, V., Yang, Q., He, G.,& Novaković, A.. (2019). Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft. in Journal of Pharmacological Sciences
Elsevier B.V.., 142(3), 101-108.
https://doi.org/10.1016/j.jphs.2019.11.006

Janković G, Marinko M, Milojević P, Stojanović I, Nenezić D, Kanjuh V, Yang Q, He G, Novaković A. Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft. in Journal of Pharmacological Sciences. 2019;142(3):101-108.
doi:10.1016/j.jphs.2019.11.006 .

Janković, Goran, Marinko, Marija, Milojević, Predrag, Stojanović, Ivan, Nenezić, Dragoslav, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, Novaković, Aleksandra, "Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft" in Journal of Pharmacological Sciences, 142, no. 3 (2019):101-108,
https://doi.org/10.1016/j.jphs.2019.11.006 . .