High concentrations of epigallocatechin gallate induce contractions of the rat aorta due to production of reactive oxygen species, activation of cyclooxygenase, production of prostanoids and stimulation of TP-receptors

This journal issue contain abstracts of the 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine 2009Abstracts for Posters: P9OBJECTIVE: Although regular consumption of green tea is believed to be beneficial for the cardiovascular system, a previous study revealed that high concentrations of the green tea catechin epigallocatechin gallate (EGCG) causes contractions of the aorta of spontaneously hypertensive rats (SHR). The present studies were aimed to investigate the mechanisms underlying these EGCG-induced contractions. METHODS & RESULTS: Isometric tension was measured in isolated aortic rings from 36-week-old male SHR. From 10-6 to 10-4 M EGCG induced concentration-dependent contractions in preparations both with and without endothelium, which were potentiated by L-NAME (inhibitor of endothelial NO synthase) and abolished by indomethacin (inhibitor of cyclooxygenases) or the thromboxane-prostanoid (TP) receptors antagonist S18886. The extracellular antioxidants SOD and catalase and the intracellular antioxidants apocynin, DETCA and deferoxamine, but not tiron partly reduced the response, while the combined treatment with all intracellular antioxidants abolished the contractions. The release of prostanoids end-products [including prostaglandin F1α, prostaglandin F2α and thromboxane B2] was significantly increased by EGCG as measured by enzyme immunoassay kits. The intracellular reactive oxygen species (ROS) concentration was measured by confocal microscopy. A burst of ROS was observed upon exposure to a 10-4 M of EGCG, which was unaffected by indomethacin or S18886, but was attenuated in the presence of antioxidants. DISCUSSION & CONCLUSIONS: In the rat aorta, high concentrations of EGCG induce contractions through the production of ROS, activation of cyclooxygenase, production of prostanoids and stimulation of TP receptors. The production of ROS is the initial step, and can be attributed to pro-oxidant effects of EGCG. This burst of ROS leads to the activation of cyclooxygenases in both the endothelium and the vascular smooth muscle, followed by the production of prostanoids. These prostanoids in turn stimulated TP receptors and finally caused contraction.link_to_OA_fulltex