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dc.creatorNovaković, Aleksandra
dc.creatorMarinko, Marija
dc.creatorVranić, Aleksandra
dc.creatorJanković, Goran
dc.creatorMilojević, Predrag
dc.creatorStojanović, Ivan
dc.creatorNenezić, Dragoslav
dc.creatorUgrešić, Nenad
dc.creatorKanjuh, Vladimir
dc.creatorYang, Qin
dc.creatorHe, Guo-Wei
dc.date.accessioned2019-09-02T11:48:01Z
dc.date.available2019-09-02T11:48:01Z
dc.date.issued2015
dc.identifier.issn0014-2999
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/2439
dc.description.abstractEvidences have suggested that flavanol compound (-)-epicatechin is associated with reduced risk of cardiovascular diseases. One of the mechanisms of its cardioprotective effect is vasodilation. However, the exact mechanisms by which (-)-epicatechin causes vasodilation are not yet clearly defined. The aims of the present study were to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human internal mammary artery (HIMA) and to determine the mechanisms underlying its vasorelaxation. Our results showed that (-)-epicatechin induced a concentration-dependent relaxation of RNA rings pre-contracted by phenylephrine. Among the K+ channel blockers, 4-aminopyricline (4-AP) and margatoxin, blockers of voltage gated K+ (K-V) channels, and glibenclamide, a selective ATP sensitive K+ (K-ATP,) channels blocker, partly inhibited the (-)-epicatechin-induced relaxation of HIMA, while iberiotoxin, a most selective blocker of large conductance Ca2+-activated K+ channels (BKCa), almost completely inhibited the relaxation. In rings pre-contracted by 80 mM K+, (-)-epicatechin induced partial relaxation of HIMA, whereas in Ca2+-free medium, (-)-epicatechin completely relaxed HIMA rings pre-contracted by phenylephrine and caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor, slightly antagonized (-)-epicatechin-induced relaxation of HIMA pre-contracted by phenylephrine. These results suggest that (-)-epicatechin induces strong endothelium independent relaxation of HIMA pre-contracted by phenylephrine whilst 4-AP- and rnargatoxin-sensitive K-V channels, as well as BKCa and K-ATP channels, located in vascular smooth muscle, mediate this relaxation. In addition, it seems that (-)-epicatechin could inhibit influx of extracellular Ca2+, interfere with intracellular Ca2+ release and re uptake by the sarcoplasmic reticulum.en
dc.publisherElsevier Science BV, Amsterdam
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175088/RS//
dc.rightsrestrictedAccess
dc.sourceEuropean Journal of Pharmacology
dc.titleMechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechinen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractМаринко, Марија; Yанг, Qин; Кањух, Владимир; Угрешић, Ненад; Хе, Гуо-Wеи; Ненезић, Драгослав; Новаковић, Aлександра; Стојановић, Иван; Милојевић, Предраг; Јанковић, Горан; Вранић, Aлександра;
dc.citation.volume762
dc.citation.spage306
dc.citation.epage312
dc.citation.other762: 306-312
dc.citation.rankM22
dc.identifier.wos000359711100038
dc.identifier.doi10.1016/j.ejphar.2015.05.066
dc.identifier.pmid26049011
dc.identifier.scopus2-s2.0-84931273854
dc.type.versionpublishedVersion


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