Distinct signalling mechanisms are involved in the dissimilar myocardial and coronary effects elicited by quercetin and myricetin, two red wine flavonols

Angelone, T.; Pasqua, T.; Di Majo, D.; Quintieri, A.M.; Filice, E.; Amodio, N.; Tota, B.; Giammanco, M.; Cerra, M.C.

doi:10.1016/j.numecd.2009.10.011

« Previous Next »Nutrition, Metabolism & Cardiovascular Diseases
Volume 21, Issue 5 , Pages 362-371, May 2011

Distinct signalling mechanisms are involved in the dissimilar myocardial and coronary effects elicited by quercetin and myricetin, two red wine flavonols

T. Angelone
- Lab of Cardiovascular Pathophysiology, Dept of Cell Biology, University of Calabria, 87030 Arcavacata di Rende (CS), Italy
- Corresponding author. Tel./fax: +39 (0)984492906.
T. Pasqua
- Lab of Cardiovascular Pathophysiology, Dept of Cell Biology, University of Calabria, 87030 Arcavacata di Rende (CS), Italy
D. Di Majo
- Dept. of Medicine, Pneumology, Physiology and Human Nutrition, University of Palermo, Palermo, Italy
A.M. Quintieri
- Dept. of Pharmaco-Biology, University of Calabria, 87030 Arcavacata di Rende (CS), Italy
E. Filice
- Dept. of Pharmaco-Biology, University of Calabria, 87030 Arcavacata di Rende (CS), Italy
N. Amodio
- Dept. of Experimental and Clinical Medicine, University of Catanzaro Magna Græcia, Catanzaro, Italy
B. Tota
- Lab of Cardiovascular Pathophysiology, Dept of Cell Biology, University of Calabria, 87030 Arcavacata di Rende (CS), Italy
M. Giammanco
- Dept. of Medicine, Pneumology, Physiology and Human Nutrition, University of Palermo, Palermo, Italy
M.C. Cerra
- Lab of Cardiovascular Pathophysiology, Dept of Cell Biology, University of Calabria, 87030 Arcavacata di Rende (CS), Italy
- Dept. of Pharmaco-Biology, University of Calabria, 87030 Arcavacata di Rende (CS), Italy

Received 29 July 2009; received in revised form 29 September 2009; accepted 19 October 2009. published online 22 January 2010.

Abstract

Background and Aims

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.

Methods and 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.

Keywords: Quercetin, Myricetin, Myocardial contractility, Vasoreactivity, Nitric oxide