Whereas studies involving animal models of cardiovascular disease demonstrated 
that resveratrol is able to inhibit hypertrophic growth, the mechanisms involved 
have not been elucidated. Because studies in cells other than cardiomyocytes 
revealed that AMP-activated protein kinase (AMPK) and Akt are affected by 
resveratrol, we hypothesized that resveratrol prevents cardiac myocyte 
hypertrophy via these two kinase systems. Herein, we demonstrate that 
resveratrol reduces phenylephrine-induced protein synthesis and cell growth in 
rat cardiac myocytes via alterations of intracellular pathways involved in 
controlling protein synthesis (p70S6 kinase and eukaryotic elongation factor-2). 
Additionally, we demonstrate that resveratrol negatively regulates the 
calcineurin-nuclear factor of activated T cells pathway thus modifying a 
critical component of the transcriptional mechanism involved in pathological 
cardiac hypertrophy. Our data also indicate that these effects of resveratrol 
are mediated via AMPK activation and Akt inhibition, and in the case of AMPK, is 
dependent on the presence of the AMPK kinase, LKB1. Taken together, our data 
suggest that resveratrol exerts anti-hypertrophic effects by activating AMPK via 
LKB1 and inhibiting Akt, thus suppressing protein synthesis and gene 
transcription.