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 HIMA rings pre-contracted by phenylephrine. Among the K + channel blockers, 4-aminopyridine (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 Ca 2+ -activated K + channels (BK Ca), almost completely inhibited the relaxation. In rings pre-contracted by 80 mM K +, (-)-epicatechin induced partial relaxation of HIMA, whereas in Ca 2+ -free medium, (-)-epicatechin completely relaxed HIMA rings pre-contracted by phenylephrine and caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca 2+ -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 margatoxin-sensitive K V channels, as well as BK Ca and K ATP channels, located in vascular smooth muscle, mediate this relaxation. In addition, it seems that (-)-epicatechin could inhibit influx of extracellular Ca 2+, interfere with intracellular Ca 2+ release and re-uptake by the sarcoplasmic reticulum.
CITATION STYLE
Novakovic, A., Marinko, M., Vranic, A., Jankovic, G., Milojevic, P., Stojanovic, I., … He, G. W. (2015). Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin. European Journal of Pharmacology, 762, 306–312. https://doi.org/10.1016/j.ejphar.2015.05.066
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