Rapid, non-genomic vascular actions of genistein suggests a phytoestrogen receptor

Abstract

Genistein, a phytoestrogen rich in soy beans and soy products, was reported to be a vasorelaxant. This study examined the receptor and related signaling pathways in the rapid vascular actions of genistein. Isometric tension was measured in isolated aortic rings from male spontaneous hypertensive rats (SHR). Acute exposure to genistein at 10 µM, a concentration with no direct relaxation effect, potentiated acetylcholine (ACh)-induced relaxation and reduced ACh-induced contraction. Both actions were insensitive to 10 µM actionmycin D (transcription inhibitor) and 10 µM cycloheximide (translation inhibitor). The potentiation of ACh-induced relaxation by genistein was inhibited by 10 µM NF023 and 10 µM GP antagonist-2A, the selective Gi/o and Gq{alpha}-subunit antagonists respectively, but not by 10 µM NF449, a selective Gs{alpha}-subunit antagonist. Interestingly, NF023, NF449 and GP antagonist-2A did not alter the inhibitory effect of genistein on ACh-induced contraction. These results demonstrate that rapid vascular actions of genistein in modulating ACh-induced relaxation and contraction responses in SHR are mediated by non-genomic pathways. Furthermore, involvement of G-proteins in the enhancement of ACh-induced relaxation by genistein suggests that genistein exerts its effect through a putative G-protein coupled phytoestrogen receptor. (Supported by the Research Grant Council of Hong Kong)