Endothelium/nitric oxide mechanism mediates vasorelaxation and counteracts vasoconstriction induced by low concentrations of flavanols

PURPOSE: At relatively low concentrations, flavanols induce inconsistent effects on isolated arterial tone, sometimes explained as being due to a structure-activity relationship. The aim of our study was to investigate the effects of two flavanols at different doses on arterial functional state. METHODS: The effects of two catechins, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin (EP), on rat-isolated aorta tone were investigated on resting tension and on precontracted preparations, both in the presence and in the absence of endothelium. RESULTS: At resting tension, endothelium-intact preparations, EGCG and EP (0.01-10 μM), induced a slight concentration-dependent, non-significant contraction. On endothelium-denuded preparations, both EGCG and EP induced a concentration-dependent contraction (significance at 0.1 and 1 μM concentrations of the two compounds, respectively). In phenylephrine (PE) (1 μM) precontracted, endothelium-intact preparations, EGCG and EP (0.01-10 μM), induced a concentration-dependent vasorelaxation, reaching significance at 1 μM concentration of both agonists. On endothelium-denuded preparations, EGCG and EP did not significantly affect PE (0.3 μM)-induced tone. In endothelium-intact precontracted preparations, Nω nitro-L: -arginine (L-NNA), a nitric oxide synthase (NOS) activity inhibitor, abolished the vasorelaxant effect of EGCG and EP (0.01-10 μM). At high concentrations, EGCG and EP (100 μM) elicited a marked relaxation. This was significantly larger in the presence than in the absence of endothelium or in the presence of L-NNA. CONCLUSIONS: Our findings highlight the important role played by an endothelium/NO-mechanism in the regulation of basal tone and in both mediating vasorelaxation and counteracting vasoconstriction induced by low concentrations of flavanols in rat thoracic aorta.