Green tea attenuates angiotensin II-induced cardiac hypertrophy in rats by modulating reactive oxygen species production and the Src/epidermal growth factor receptor/Akt signaling pathway

We previously documented a clear-cut antihypertensive effect of green teat extract (GTE), which was associated with correction of endothelial dysfunction and prevention of left ventricular hypertrophy in an angiotensin II (Ang II)-dependent model of hypertension, but the molecular mechanisms remain to be defined. As several effects of Ang II involve production of reactive oxygen species (ROS) and activation of 2nd messengers, such as mitoger-activated protein I I and Akt we investigated the effect of GTE on these signal trarsduction pathways in Ang II-treated cats. Rats were treated for 2 wk with Ang II infusion 700 mu g.kg(1)d(1);n = 6, via osmotic minipumps), Ang II plus GTE (6 g/L) dissolved in the drinking water, n 6), or vehicle (n 6) to serve as controls. Blood pressure was monitored by telemetry throughout the study. The activation and expression of NAD(P)H oxidase subunits, protein C isoforms, Sire, epidermal growth factor receptor (EGFR) Akt, and MAPK were determined in the heart in vitro through immunoprecipitation and western blot analysis with specific antibodies, I oxidase enzymatic activity was measured by cytochrome c reduction assay. GTE blunted Ang II-induced blood pressure increase and cardiac hypertrophy. In Ang II-treated rats, GTE decreased the expression of the I oxidase subunit gp91(phox) and the translocation of Rac-1, as well as I oxidase enzymatic activity. Furthermore, it specifically reduced Arg II-induced Src, EGFR and Akt phosphorylation. These results show that GTE blunts Ang II-induced cardiac hypertrophy specifically by regulating I production and the Src/EGFR/Akt signaling pathway activated by Ang II.