Involvement of thromboxane A(2) in the endothelium-dependent contractions induced by myricetin in rat isolated aorta

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.