Pparα/No Involves In The Effect Of Berberine On The Vascular Smooth Muscle Cells Proliferation Induced By Angiotensin IV

Objective: To investigate the effects of peroxisome proliferator- activated receptor-α(PPARα) / nitric oxide (NO) pathway on the vascular smooth muscle cells (VSMCs) proliferation induced by angiotensinⅣ(AngⅣ),and the role and the mechanisms of berberine on VSMCs proliferation.Methods: Primary VSMCs were cultured by the tissue explants method. The effect of the VSMCs proliferation was determined by MTT assay and protein content. The expressions of mRNA and protein were detected by real-time RT-PCR and Western blotting.The nitric oxide synthase(NOS)activity and NO concentration in culture media were determined by the spectrophotometry and nitrate reduction method, respectively.Results: Compared with control, AngⅣ(0.01, 0.1, 1 nmol/L) significantly stimulated the proliferation of VSMCs, which were elevated by berberine in a concentration-dependent manner (from 10 to 100μmol·L^-1), and reduced the expressions of PPARαat both mRNA and protein levels (P<0.05), and decreased also eNOS mRNA expression, NOS activity and NO release (P<0.01), Fenofibrate and L-arginine had similar effects with berberine (P<0.05). A selective PPARαantagonist, MK 886 and a NOS inhibitor, N^G-nitro-L-arginine-methyl ester, could abolish the effects of berberine (P<0.05).Conclusions: Our results suggest that AngⅣcan induce VSMCs proliferation, which PPARα/NO signaling pathway downregulate may be involved in it. BBR can inhibit VSMCs proliferation induced by AngⅣ, which may be mediated by upregulating the expression of PPARα, and elevating the expression and activity of eNOS, increasing the release of NO, finally.