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

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 ß-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 ß1/ß2-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.

Omega 3 fatty acids: biological activity and effects on human health.

Polyunsaturated fatty acids (PUFAs) have an important role in human diet, both for the prevention and the therapy of different pathologies. In this review, a critical evaluation of PUFAs dietary sources and biological functions in human organism has been done. In particular, the efficacy of omega-3 fatty acids in the improvement of the lipidic pattern and in the excitability of myocardium has been analyzed, and, therefore, their usefulness in the prevention of cardiovascular diseases and postinfarction arrhythmias. As PUFAs are precursors of prostaglandins and leucotriens, which are involved in phlogosis and immune response, a diet rich in fish oil reduces the production of PGE2 involved in many phlogosis events. Moreover, an increase in the eicosapentaenoic acid (EPA) intake leads to a reduction in the production of inflammatory cytokines (interleukin 1, 2, 6 and tumor necrosis factor); so, it is important to use omega-3 in chronic inflammatory diseases, as the rheumatoid arthritis. It seems that omega-3 could prevent the onset of hormone-dependent tumours (i.e. breast and prostatic cancer); in vitro observations, in fact, have shown that the PG of the series 2, derived from omega-6, have a carcinogenic action; instead, the anticancer effect of omega-3 could derive from their effect in antagonizing the formation of such PG; it can be useful, therefore, to increase the dietary omega-3/omega-6 ratio. Moreover, the effects of omega-3 on the anatomic and functional central nervous system development and of their possible therapeutical use in some psychiatric pathologies were evaluated.