Abstract
The role of PKC and Na+/K+-ATPase in the vascular smooth muscle responses induced by the bioflavonoid myricetin was investigated. KCl induced a concentration-dependent relaxation in arteries exposed to K+-free solution that was mainly mediated by an activation of Na+/K+-ATPase. Myricetin (50 μM) partially inhibited this vasorelaxant effect induced by KCl in intact rings, being unaffected in the endothelium-denuded rings. This inhibitory effect induced by myricetin was suppressed by the PGH2-TXA2 receptor antagonist, SQ 29,548, and the PKC inhibitor, staurosporine. Myricetin also induced an endothelium-dependent contractile response which was increased in the presence of PMA and reduced by staurosporine. In conclusion, myricetin both modulates Na+/K+-ATPase-induced vasodilatation acting as a functional inhibitor of Na+/K+-ATPase activity and activates protein kinases, including PKC, to induce contraction. These effects appear to be related to the activation of PGH2-TXA2 receptors on vascular smooth muscle by the TXA2 released from endothelium.
Abbreviations
NA:noradrenaline
NA+/K+-ATPase pump:sodium-potassium-activated ATPase
PKC:protein kinase C
PMA:phorbol 12-myristate 13-acetate
TXA2:thromboxane A2
Abstract
The role of PKC and Na+/K+-ATPase in the vascular smooth muscle responses induced by the bioflavonoid myricetin was investigated. KCl induced a concentration-dependent relaxation in arteries exposed to K+-free solution that was mainly mediated by an activation of Na+/K+-ATPase. Myricetin (50 μM) partially inhibited this vasorelaxant effect induced by KCl in intact rings, being unaffected in the endothelium-denuded rings. This inhibitory effect induced by myricetin was suppressed by the PGH2-TXA2 receptor antagonist, SQ 29,548, and the PKC inhibitor, staurosporine. Myricetin also induced an endothelium-dependent contractile response which was increased in the presence of PMA and reduced by staurosporine. In conclusion, myricetin both modulates Na+/K+-ATPase-induced vasodilatation acting as a functional inhibitor of Na+/K+-ATPase activity and activates protein kinases, including PKC, to induce contraction. These effects appear to be related to the activation of PGH2-TXA2 receptors on vascular smooth muscle by the TXA2 released from endothelium.
Abbreviations
NA:noradrenaline
NA+/K+-ATPase pump:sodium-potassium-activated ATPase
PKC:protein kinase C
PMA:phorbol 12-myristate 13-acetate
TXA2:thromboxane A2
Key words
Myricetin - flavonoids - aorta - rat - protein kinase C - Na+/K+-ATPase - thromboxane A2
Key words
Myricetin - flavonoids - aorta - rat - protein kinase C - Na+/K+-ATPase - thromboxane A2
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Prof. Dr. J. Duarte
Department of Pharmacology
School of Pharmacy
University of Granada
18071 Granada
Spain
Email: jmduarte@platon.ugr.es
Fax: +34-958-248964
