Involvement of thromboxane A2 in the endothelium-dependent contractions induced by myricetin in rat isolated aorta
Article first published online: 29 JAN 2009
1999 Nature Publishing Group
British Journal of Pharmacology
Volume 127, Issue 7, pages 1539–1544, August 1999
How to Cite
Jiménez, R., Andriambeloson, E., Duarte, J., Andriantsitohaina, R., Jiménez, J., Pérez-Vizcaino, F., Zarzuelo, A. and Tamargo, J. (1999), Involvement of thromboxane A2 in the endothelium-dependent contractions induced by myricetin in rat isolated aorta. British Journal of Pharmacology, 127: 1539–1544. doi: 10.1038/sj.bjp.0702694
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received January 26, 1999, Revised April 27, 1999, Accepted May 5, 1999)
- thromboxane A2;
- rat aorta
The present study was undertaken to analyse the mechanism of the contractile response induced by the bioflavonoid myricetin in isolated rat aortic rings.
Myricetin induced endothelium-dependent contractile responses (maximal value=21±2% of the response induced by 80 mM KCl and pD2=5.12±0.03). This effect developed slowly, reached a peak within 6 min and then declined progressively.
Myricetin-induced contractions were almost abolished by the phospholipase A2 (PLA2) inhibitor, quinacrine (10 μM), the cyclo-oxygenase inhibitor, indomethacin (10 μM), the thromboxane synthase inhibitor, dazoxiben (100 μM), the putative thromboxane A2 (TXA2)/prostaglandin endoperoxide receptor antagonist, ifetroban (3 μM). These contractions were abolished in Ca2+-free medium but were not affected by the Ca2+ channel blocker verapamil (10 μM).
In cultured bovine endothelial cells (BAEC), myricetin (50 μM) produced an increase in cytosolic free calcium ([Ca2+]i) which peaked within 1 min 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.
Myricetin (50 μM) significantly increased TXB2 production both in aortic rings with and without endothelium and in BAEC. These increases were abolished both by Ca2+-free media and by indomethacin.
Taken together, these results suggests that myricetin stimulates Ca2+ influx and subsequently triggers the activation of the PLA2 and cyclo-oxygenase pathways releasing TXA2 from the endothelium to contract rat aortic rings. The latter response occurs via the activation of Tp receptors on vascular smooth muscle cells.
British Journal of Pharmacology (1999) 127, 1539–1544; doi:10.1038/sj.bjp.0702694