Involvement of thromboxane A₂ in the endothelium‐dependent contractions induced by myricetin in rat isolated aorta

Abstract

1 The present study was undertaken to analyse the mechanism of the contractile response induced by the bio¯avonoid myricetin in isolated rat aortic rings. 2 Myricetin induced endothelium-dependent contractile responses (maximal value=21+2% of the response induced by 80 mM KCl and pD 2 =5.12+0.03). This e ect developed slowly, reached a peak within 6 min and then declined progressively. 3 Myricetin-induced contractions were almost abolished by the phospholipase A 2 (PLA 2 ) inhibitor, quinacrine (10 mM), the cyclo-oxygenase inhibitor, indomethacin (10 mM), the thromboxane synthase inhibitor, dazoxiben (100 mM), the putative thromboxane A 2 (TXA 2 )/prostaglandin endoperoxide receptor antagonist, ifetroban (3 mM). These contractions were abolished in Ca 2+ -free medium but were not a ected by the Ca 2+ channel blocker verapamil (10 mM). 4 In cultured bovine endothelial cells (BAEC), myricetin (50 mM) produced an increase in cytosolic free calcium ([Ca 2+ ] i ) which peaked within 1 min and remained sustained for 6 min, as determined by the¯uorescent probe fura 2. This rise in [Ca 2+ ] i was abolished after removal of extracellular Ca 2+ in the medium. 5 Myricetin (50 mM) signi®cantly increased TXB 2 production both in aortic rings with and without endothelium and in BAEC. These increases were abolished both by Ca 2+ -free media and by indomethacin. 6 Taken together, these results suggests that myricetin stimulates Ca 2+ in¯ux and subsequently triggers the activation of the PLA 2 and cyclo-oxygenase pathways releasing TXA 2 from the endothelium to contract rat aortic rings. The latter response occurs via the activation of T p receptors on vascular smooth muscle cells.

Orchidectomy Modulates α₂-Adrenoceptor Reactivity in Rat Mesenteric Artery through Increased Thromboxane A₂ Formation

“…On the other hand, the cellular source of TXA 2 production is not well established, since TXA 2 release from endothelial [36, 37] and smooth muscle [38, 39] cells has been reported. To study the location of TXA 2 production, we first analyzed the effect of the COX inhibitors on the clonidine-induced vasoconstriction in endothelially denuded vessels.…”

LPS exacerbates endothelin-1 induced activation of cytosolic phospholipase A2 and thromboxane A2 production from Kupffer cells of the prefibrotic rat liver

“…Productions of TXA 2 depend on a number of key enzymes in its biosynthesis pathway [20][21][22][23][24][25][26]. Phospholipase A 2 (PLA 2 ) catalyzes the hydrolysis of plasma membrane phospholipids to arachidonic acid (AA).…”

Effects of the Dietary Flavonoid Chrysin in Isolated Rat Mesenteric Vascular Bed

“…1) is present in honey and propolis [2]and in low concentrations in fruits, vegetables and beverages [3]. Most flavonoids have been reported to modulate the vascular tone [4, 5, 6, 7, 8, 9]. In vitro experiments in isolated rat aorta have revealed that chrysin was able to induce endothelium and NO-dependent vasorelaxation, mediated by the prevention of superoxide anion (O – 2 )-induced inactivation of endothelium derived NO and also by the potentiation of guanosine 3′,5′-cyclic monophosphate (cGMP)-induced vasodilatation [10].…”