(-)-Epigallocatechin-3-gallate induces contraction of the rat aorta by a calcium influx-dependent mechanism.

Although the consumption of tea has been associated with beneficial cardiovascular effects, (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin in this beverage has shown seemingly contradictory actions on vascular tissues, for example vasorelaxant activity that could contribute favourably to prevention of cardiovascular disease, and contractile activity that could act in the opposite direction. The purpose of the present work was to study the contractile effects of EGCG on isolated rat thoracic aorta rings and its effects on the cytosolic free [Ca(2+)] (Ca(2+)) measured with fura-2 in cultured rat aortic smooth muscle cell line. In partially depolarised (15 mM KCl) aortic rings EGCG (30-300 microM), (+/-)-BAY K 8644 (0.1 microM) and thapsigargin (1 microM) induced a Ca(2+)-dependent, endothelium-independent contraction associated with Ca(2+) elevation in RASMC. EGCG enhanced the responses elicited by (+/-)-BAY K 8644 and thapsigargin both in aortic rings and in RASMC. Nifedipine totally inhibited the (+/-)-BAY K 8644-induced contraction, but only partially blocked the contractile responses to EGCG and thapsigargin, while SKF 96365 abolished both responses. The effects of these channel blockers were associated with a decrease in Ca(2+) in RASMC. Re-introduction of Ca(2+) in the medium after depletion of intracellular Ca(2+) stores with thapsigargin in a Ca(2+)-free solution elicited a contraction of aortic rings and an increase in Ca(2+) in RASMC. In both cases, this response was partially sensitive to nifedipine, abolished by SKF 96365 and clearly enhanced by EGCG. These results suggest that EGCG induces a transient endothelium-independent contraction in the rat aorta, probably by increasing smooth vascular cell membrane permeability to Ca(2+) through both non-specific and dihydropyridine-sensitive Ca(2+) channels.