OBJECTIVETo observe the effect and mechanism of resveratrol on cardiac fibroblast (cFs) proliferation induced by angiotensin II (Ang II).

METHODSThe in vitro cFs proliferation model was established by stimulating cultured cFs of new born rats with Ang II by differential attachment method. Cell proliferation was measured by MTT assay, and the effect of resveratrol, L-NAME and ODQ on cell proliferation were observed respectively. Besides, the hypertrophic response of cFs was estimated by measuring expressions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNA, with the levels of ANP and BNP in culture medium determined by radioimmunoassay and ELISA respectively; and their mRNA expressions determined by reverse transcription polymerase chain reaction (RT-PCR). Level of nitric oxide (NO) in the culture medium was measured by Griess reagent; nitric oxide synthase (NOS) level by chemical colorimetric method; and cGMP by radioimmunoassay.

RESULTSResveratrol at the dose of 25-100 micromol/L inhibited cFs proliferation in a time and dose dependent manner, which could be partially blocked by pretreatment with L-NAME or ODQ. NO and cGMP levels increased, ANP, BNP levels and their mRNA expression lowered after resveratrol treatment.

CONCLUSIONResveratrol in a definite concentration range could inhibit cFs proliferation and hypertrophic response induced by Ang II, up-regulating the signal pathway of NO and cGMP might be one of the acting paths of the inhibitory effects.