title: Distinct signalling mechanisms are involved in the dissimilar myocardial and coronary effects elicited by quercetin and myricetin, two red wine flavonols.
abstract: OBJECTIVE
  Moderate red wine consumption associates with lower incidence of cardiovascular diseases. Attention to the source of this cardioprotection was focused on flavonoids, the non-alcoholic component of the red wine, whose intake inversely correlates with adverse cardiovascular events. We analysed whether two red wine flavonoids, quercetin and myricetin, affect mammalian basal myocardial and coronary function.
  
  
  RESULTS
  Quercetin and myricetin effects were evaluated on isolated and Langendorff perfused rat hearts under both basal conditions and α- and β-adrenergic stimulation. The intracellular signalling involved in the effects of these flavonoids was analysed on perfused hearts and by western blotting on cardiac and HUVEC extracts. Quercetin induced biphasic inotropic and lusitropic effects, positive at lower concentrations and negative at higher concentrations. Contrarily, Myricetin elicits coronary dilation, without affecting contractility and relaxation. Simultaneous administration of the two flavonoids only induced vasodilation. Quercetin-elicited positive inotropism and lusitropism depend on β1/β2-adrenergic receptors and associate with increased intracellular cAMP, while the negative inotropism and lusitropism observed at higher concentrations were α-adrenergic-dependent. NOS inhibition abolished Myricetin-elicited vasodilation, also inducing Akt, ERK1/2 and eNOS phosphorylation in both ventricles and HUVEC. Myricetin-dependent vasodilation increases intracellular cGMP and is abolished by triton X-100.
  
  
  CONCLUSIONS
  The cardiomodulation elicited on basal mechanical performance by quercetin and the selective vasodilation induced by myricetin point to these flavonoids as potent cardioactive principles, able to protect the heart in the presence of cardiovascular diseases.
authors.affiliation: Lab of Cardiovascular Pathophysiology, Dept of Cell Biology, University of Calabria, 87030 Arcavacata di Rende (CS), Italy. t.angelone@unical.it
authors.forename: T
authors.initials: T
authors.lastname: Angelone
authors.forename: T
authors.initials: T
authors.lastname: Pasqua
authors.forename: D
authors.initials: D
authors.lastname: Di Majo
authors.forename: A M
authors.initials: AM
authors.lastname: Quintieri
authors.forename: E
authors.initials: E
authors.lastname: Filice
authors.forename: N
authors.initials: N
authors.lastname: Amodio
authors.forename: B
authors.initials: B
authors.lastname: Tota
authors.forename: M
authors.initials: M
authors.lastname: Giammanco
authors.forename: M C
authors.initials: MC
authors.lastname: Cerra
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D017830:Octoxynol; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014664:Vasodilation / Q000187:drug effects; D014920:Wine
chemical_list: D000975:Antioxidants; D005419:Flavonoids; C040015:myricetin; D017830:Octoxynol; D011794:Quercetin