title: 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 bioflavonoid 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 pD2=5.12+/-0.03). This effect developed slowly, reached a peak within 6 min and then declined progressively. 3. Myricetin-induced contractions were almost abolished by the phospholipase A2 (PLA2) inhibitor, quinacrine (10 microM), the cyclo-oxygenase inhibitor, indomethacin (10 microM), the thromboxane synthase inhibitor, dazoxiben (100 microM), the putative thromboxane A2 (TXA2)/prostaglandin endoperoxide receptor antagonist, ifetroban (3 microM). These contractions were abolished in Ca2+-free medium but were not affected by the Ca2+ channel blocker verapamil (10 microM). 4. In cultured bovine endothelial cells (BAEC), myricetin (50 microM) 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. 5. Myricetin (50 microM) 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. 6. 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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Granada, 18071 Granada, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Jiménez
authors.forename: E
authors.initials: E
authors.lastname: Andriambeloson
authors.forename: J
authors.initials: J
authors.lastname: Duarte
authors.forename: R
authors.initials: R
authors.lastname: Andriantsitohaina
authors.forename: J
authors.initials: J
authors.lastname: Jiménez
authors.forename: F
authors.initials: F
authors.lastname: Pérez-Vizcaino
authors.forename: A
authors.initials: A
authors.lastname: Zarzuelo
authors.forename: J
authors.initials: J
authors.lastname: Tamargo
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D016718:Arachidonic Acid / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000502:physiology*; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D005419:Flavonoids; D016718:Arachidonic Acid; D009569:Nitric Oxide; D013929:Thromboxane B2; D013928:Thromboxane A2; C040015:myricetin; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D010741:Phospholipases A; D054467:Phospholipases A2; D019331:NG-Nitroarginine Methyl Ester