Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin
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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
- Elsevier Science BV, Amsterdam