OBJECTIVETo explore the effects of adrenomedullin (ADM) on Angiotensin II (AngII)-induced collagen synthesis in cultured rat vascular adventitial fibroblasts.

METHODSRat vascular adventitial fibroblasts were cultured in vitro. ADM produced and secreted from adventitia in the presence of AngII was detected by radioimmunoassay, type I, III collagen contents in adventitia fibroblasts were measured by ELISA and the expressions of TGFbeta1 and MMP-2 were determined by RT-PCR and Western blotting.

RESULTSAngII significantly induced ADM secretion in adventitial fibroblasts in a dose-dependent manner. These effects could be reduced by 45%, 3% and 46%, through pre-treatment with Losartan, PD123319 or both, respectively for 30 min in culture medium. The AngII-induced type I, III collagen secretion in adventitial fibroblasts was significantly reduced by AMD in a dose-dependent manner, (P < 0.01) while ADM agonist ADM(22 - 52) significantly potentiated the effect of AngII; ADM also reduced AngII-induced expression of TGFbeta1 at mRNA and protein levels in a dose-dependent manner. AngII reduced the expression of MMP-2 at mRNA and protein levels in adventitial fibroblasts and these effects could be reversed by AMD (10(-8) mol/L).

CONCLUSIONAngII stimulated ADM secretion in adventitia fibroblasts, ADM in turn can inhibit AngII-induced type I, III collagen synthesis in adventitial fibroblasts probably by downregulating the TGFbeta1 expression and upregulating MMP-2 expression. ADM therefore served as an antifibrotic factor in vascular remodeling process.