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Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin

Authorized Users Only
2015
Authors
Novaković, Aleksandra
Marinko, Marija
Vranić, Aleksandra
Janković, Goran
Milojević, Predrag
Stojanović, Ivan
Nenezić, Dragoslav
Ugrešić, Nenad
Kanjuh, Vladimir
Yang, Qin
He, Guo-Wei
Article (Published version)
Metadata
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Abstract
Evidences 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), almos...t 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.

Source:
European Journal of Pharmacology, 2015, 762, 306-312
Publisher:
  • Elsevier Science BV, Amsterdam
Funding / projects:
  • Investigation of the Effect and Mechanism of Action of Different Vasodilator Substances on the Human Bypass Grafts (RS-175088)

DOI: 10.1016/j.ejphar.2015.05.066

ISSN: 0014-2999

PubMed: 26049011

WoS: 000359711100038

Scopus: 2-s2.0-84931273854
[ Google Scholar ]
23
22
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/2439
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Novaković, Aleksandra
AU  - Marinko, Marija
AU  - Vranić, Aleksandra
AU  - Janković, Goran
AU  - Milojević, Predrag
AU  - Stojanović, Ivan
AU  - Nenezić, Dragoslav
AU  - Ugrešić, Nenad
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2439
AB  - Evidences 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.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmacology
T1  - Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin
VL  - 762
SP  - 306
EP  - 312
DO  - 10.1016/j.ejphar.2015.05.066
ER  - 
@article{
author = "Novaković, Aleksandra and Marinko, Marija and Vranić, Aleksandra and Janković, Goran and Milojević, Predrag and Stojanović, Ivan and Nenezić, Dragoslav and Ugrešić, Nenad and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei",
year = "2015",
abstract = "Evidences 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.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmacology",
title = "Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin",
volume = "762",
pages = "306-312",
doi = "10.1016/j.ejphar.2015.05.066"
}
Novaković, A., Marinko, M., Vranić, A., Janković, G., Milojević, P., Stojanović, I., Nenezić, D., Ugrešić, N., Kanjuh, V., Yang, Q.,& He, G.. (2015). Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin. in European Journal of Pharmacology
Elsevier Science BV, Amsterdam., 762, 306-312.
https://doi.org/10.1016/j.ejphar.2015.05.066
Novaković A, Marinko M, Vranić A, Janković G, Milojević P, Stojanović I, Nenezić D, Ugrešić N, Kanjuh V, Yang Q, He G. Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin. in European Journal of Pharmacology. 2015;762:306-312.
doi:10.1016/j.ejphar.2015.05.066 .
Novaković, Aleksandra, Marinko, Marija, Vranić, Aleksandra, Janković, Goran, Milojević, Predrag, Stojanović, Ivan, Nenezić, Dragoslav, Ugrešić, Nenad, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, "Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin" in European Journal of Pharmacology, 762 (2015):306-312,
https://doi.org/10.1016/j.ejphar.2015.05.066 . .

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