R. Jimenez et al., Involvement of thromboxane A(2) in the endothelium-dependent contractions induced by myricetin in rat isolated aorta, BR J PHARM, 127(7), 1999, pp. 1539-1544
1 The present study was undertaken to analyse the mechanism of the contract
ile response induced by the bioflavonoid myricetin in isolated rat aortic r
ings.
2 Myricetin induced endothelium-dependent contractile responses (maximal va
lue = 21 +/- 2% of the response induced by 80 mM KCl and pD(2) = 5.12 +/- 0
.03). This effect developed slowly, reached a peak within 6 min and then de
clined progressively.
3 Myricetin-induced contractions were almost abolished by the phospholipase
A(2) (PLA(2)) inhibitor, quinacrine (10 mu M), the cyclo-oxygenase inhibit
or, indomethacin (10 mu M), the thromboxane synthase inhibitor, dazoxiben (
100 mu M), the putative thromboxane A(2) (TXA(2))/prostaglandin endoperoxid
e receptor antagonist, ifetroban (3 mu M). These contractions were abolishe
d in Ca2+-free medium but were not affected by the Ca2+ channel blocker ver
apamil (10 mu M).
4 In cultured bovine endothelial cells (BAEC), myricetin (50 mu M) produced
an increase in cytosolic free calcium ([Ca2+](i)) which peaked within 1 mi
n and remained sustained for 6 min, as determined by the fluorescent probe
fura 2. This rise in [Ca2+](i) was abolished after removal of extracellular
Ca2+ in the medium.
5 Myricetin (50 mu M) significantly increased TXB2 production both in aorti
c rings with and without endothelium and in BAEC. These increases were abol
ished both by Ca2+-free media and by indomethacin.
6 Taken together, these results suggests that myricetin stimulates Ca2+ inf
lux and subsequently triggers the activation of the PLA(2) and cyclo-oxygen
ase pathways releasing TXA(2) from the endothelium to contract rat aortic r
ings. The latter response occurs via the activation of T-p receptors on vas
cular smooth muscle cells.