Effect of green tea extract on cardiac hypertrophy following 5/6 nephrectomy in the rat.

BACKGROUND Left ventricular hypertrophy commonly complicates chronic renal failure. We have observed that at least one pathway of left ventricular hypertrophy appears to involve signaling through reactive oxygen species (ROS). Green tea is a substance that appears to have substantial antioxidant activity, yet is safe and is currently widely used. We, therefore, studied whether green tea supplementation could attenuate the development of left ventricular hypertrophy in an animal model of chronic renal failure. METHODS Male Sprague-Dawley rats were subjected to sham or remnant kidney surgery and given green tea extract (0.1% and 0.25%) or plain drinking water for the next 4 weeks. Heart weight, body weight, and cardiac Na-K-ATPase activity were measured at the end of this period. To further test our hypothesis, we performed studies in cardiac myocytes isolated from adult male Sprague-Dawley rats. We measured the generation of ROS using the oxidant sensitive dye dichlorofluorescein (DCF) as well as (3H)phenylalanine incorporation following exposure to cardiac glycosides with and without green tea extract. RESULTS Administration of green tea extract at 0.25% resulted in attenuation of left ventricular hypertrophy, hypertension, and preserved cardiac Na-K-ATPase activity in rats subjected to remnant kidney surgery (all P < 0.01). In subsequent studies performed in isolated cardiac myocytes, both ouabain and marinobufagenin (MBG) were both found to increase ROS production and (3H)phenylalanine incorporation at concentrations substantially below their inhibitor concentration (IC) 50 for the sodium pump. Addition of green tea extract prevented increases in ROS production as well as (3H)phenylalanine incorporation in these isolated cardiac myocytes. CONCLUSION Green tea extract appears to block the development of cardiac hypertrophy in experimental renal failure. Some of this effect may be related to the attenuation of hypertension, but a direct effect on cardiac myocyte ROS production and growth was also identified. Clinical studies of green tea extract in chronic renal failure patients may be warranted.