The soy phytoestrogen genistein is a potent vasorelaxant, but its mechanism of action is poorly understood. Genistein (a soy component) and DPN (2,3-bis(4-Hydroxyphenyl)-propionitrile) are beta estrogenic agonist with a beta selectivity of 40/1 and 72/1 respectively. Here, we used endothelium-denuded rat aorta to investigate the role of the cyclic AMP (cAMP)-activated, cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, and its associated Na^-K^-Cl cotransporter NKCC1. Isolated, endothelium-denuded rat aorta was contracted with phenylephrine 1 mM, and the vasorelaxant responses to genistein were investigated under conditions where CFTR was inhibited by DPC (diphenylamine-2-carboxylic acid) or glibenclamide (n=6 for compound). Both compounds fully antagonized the vasorelaxant responses to genistein, with IC50=57±18 mM and 42±11 mM for DPC and glibenclamide respectively, also the relaxing effect of DPN 50 mM was blocked at 76,4± 5,46 by DPC mM and 83,25±5,73 by Glibenclamide 100 mM. H-89, a selective protein kinase A (PKA) inhibitor, blocked the vasorelaxant responses to genistein and DPN.

These results strongly suggest that CFTR opening is involved in the vasorelaxant action of genistein and DPN, and that cAMP-dependent CFTR phosphorylation and chloride transport.

In conclusion, this paper suggest that beta estrogenic agonist have vasorelaxant effect on rat aortic smooth muscle by the path way of the pKa and CFTR.