Green tea catechins evoke a phasic contraction in rat aorta via H₂O₂‐mediated multiple‐signalling pathways

Abstract

1. The contractile effects of tea polyphenols (TP) and its four principle catechins, namely (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG), on rat aorta contractility were investigated using the isometric tension recording technique. 2. At concentrations of 5-100 mg/L, TP evoked phasic contraction of rat aorta in a concentration-dependent but endothelium-independent manner. Of the four catechins tested, EGCG and EGC (3-300 micromol/L), but not EC and ECG, mimicked the contractile response to TP, suggesting that the epigallol moiety in the B ring may be associated with the contractile effect. 3. Contractions in response to EGCG and EGC were not affected by several endogenous vasoconstrictor receptor antagonists, but could be abolished by 10 micro mol/L BAPTA-AM, a membrane-permeable Ca2+ chelator, or attenuated by removal of extracellular Ca2+, suggesting the involvement of both intracellular and extracellular Ca2+ in evoking the contraction. 4. Pretreatment with non-selective Ca2+ channel antagonists mefenamic acid (10 micro mol/L), tetrandrine (30 micro mol/L) and SKF 96365 (30 micromol/L), but not nifedipine (1 micromol/L), the selective inhibitor of voltage-dependent Ca2+ channels, inhibited the contractile responses to EGC and EGCG, indicating the involvement of Ca2+ influx via non-voltage dependent Ca2+ channels. 5. Several intracellular Ca2+ channel modulators, including procaine (5 mmol/L), dantrolene (30 micromol/L) and 2-amino ethoxydiphenyl borate (50 micromol/L; an inositol 1,4,5-trisphosphate receptor inhibitor), also inhibited EGCG- and EGC-induced contractions, thus suggesting a role of intracellular Ca2+ release in these contractions. 6. Both EGCG- and EGC-induced contractions were depressed, to different degrees, by inhibitors of several receptor-coupled enzymes, including phospholipase C, protein kinase C, phospholipase A2 and tyrosine kinase. Furthermore, both EGCG- and EGC-induced contractions were completely abolished by catalase, but not by superoxide dismutase or mannitol/dimethyl sulphoxide. 7. Taken together, these data show, for the first time, that TP and its related catechins that contain an epigallol structure in the B ring, as in EGCG and EGC, exert direct contractile effects on rat aortic smooth muscle via a H2O2-mediated pathway.

A Constituent of Green Tea, Epigallocatechin-3-gallate, Activates Endothelial Nitric Oxide Synthase by a Phosphatidylinositol-3-OH-kinase-, cAMP-dependent Protein Kinase-, and Akt-dependent Pathway and Leads to Endothelial-dependent Vasorelaxation

“…EGCG can generate H 2 O 2 (12,20), and H 2 O 2 can lead to eNOS activation and vasorelaxation in rabbit aortic rings (13). However, our experiments in the presence of catalase excluded an involvement of H 2 O 2 to the obtained results.…”

“…incubation time, dose, species) may explain these inconsistent data. A recent experimental study (20), moreover, has demonstrated that epicatechins exert vasoconstriction on resting arteries. These dual properties may partly explain the biphasic vascular effects observed in our vasoreactivity studies (transient vasoconstriction followed by sustained relaxation) in rat aortic rings after EGCG exposure.…”

Green Tea Polyphenol Causes Differential Oxidative Environments in Tumor versus Normal Epithelial Cells

“…It was reported previously that H 2 O 2 is able to induce apoptosis in certain tumor cells, and addition of exogenous catalase completely eliminated this apoptotic effect (Yang et al, 1998). Interestingly, normal rat aorta responded to EGCG by phasic contraction, which was triggered by EGCG-induced H 2 O 2 but not superoxide, possibly propelled by H 2 O 2 -triggered Ca 2ϩ release (Shen et al, 2003). Human embryonic kidney 293 cells also respond to EGCG with H 2 O 2 production in a dose-dependent pattern (Dashwood et al, 2002).…”

Identification of a PKCε-dependent regulation of myocardial contraction by epicatechin-3-gallate

“…Moreover, we identified both tea catechins and theaflavins as the active compounds of the water extracts that stimulated myocardial contraction at concentrations that have been reported in human plasma after a cup of tea (16,21). Although tea catechins were found to stimulate contraction in the isolated rat aorta or the guinea pig right atria (9,34), to our knowledge, this is the first report to show that ECG and TF 4 are two of the most effective catechins and theaflavins that increase left ventricular contraction. More importantly, we demonstrated that ECG and TF 4 stimulated myocardial contraction via pathways different from those of digitalis drugs.…”