Objective: To investigate the inhibitory effects of tetramethylpyrazinee(TMP) on angiotensin Ⅱ (Ang Ⅱ)-induced cardiomyocyte hypertrophy and the underlying mechanisms. Method: Ang Ⅱ-induced cardiomyocyte hypertrophy model was established in isolated neonatal rat ventricular myocytes. The cells were then randomly divided into 6 groups:control group

Ang Ⅱ (0.1 μmol·L-1) group

low-dose TMP (0.01 mmol·L-1) group

middle-dose TMP (0.1 mmol·L-1) group

high-dose TMP (1 mmol·L-1) group

pyrolidine dithiocarbamate(PDTC

a NF-κB inhibitor

100 μmol·L-1) group. After 24 h treatment

cardiomyocytes were harvested to measure total protein content by Lowry's method

β-myosin heavy chain (β-MHC) mRNA expression by Real-time PCR

and NF-κB content by Western blotting. Result: Ang Ⅱ induced cardiomyocyte hypertrophy characterized by increased total protein content [Ang Ⅱ groupg(296.7±27.6) mg·L-1;control group(184.3±11.6) mg L-1

P<0.05]·L-1;control group(184.3±11.6) mg·L-1

P<0.05] and enhanced β-MHC mRNA expression (Ang Ⅱ group 0.936±0.059;control group 0.496±0.030

P<0.05)

while TMP significantly inhibited Ang Ⅱ-induced hypertrophic growth in a dose-dependent manner. Meanwhile

TMP (1 mmol·L-1) also attenuated Ang Ⅱ-induced increase in phosphorylated NF-κB (Ang Ⅱ group 0.861±0.065;TMP group 0.655±0.052

P<0.05) and I-κB protein content (Ang Ⅱ group 0.785±0.042;TMP group 0.525±0.045

P<0.05) in cardiomyocytes. Furthermore

inhibition of NF-κB by the specific inhibitor PDTC markedly suppressed Ang Ⅱ-induced hypertrophic responses. Conclusion: Our findings suggested that TMP inhibits Ang Ⅱ-induced cardiomyocyte hypertrophy through suppression of NF-κB pathway

which might contribute to the protective role of TMP in cardiac diseases.