Chronic administration of genistein improves endothelial dysfunction in spontaneously hypertensive rats: involvement of eNOS, caveolin and calmodulin expression and NADPH oxidase activity

Abstract

The soya-derived phytoestrogen genistein has been suggested to be protective in cardiovascular diseases. In the present study, we have analysed whether chronic oral genistein might influence endothelial function in male SHRs (spontaneously hypertensive rats) via ERs (oestrogen receptors), changes in eNOS (endothelial NO synthase) activity and vascular O(2)(-) (superoxide) production. Rats (23-weeks old) were divided into the following groups: WKY (Wistar-Kyoto)-vehicle, SHR-vehicle, WKY-genistein (10 mg.kg(-1) of body weight.day(-1)); SHR-genistein; SHR-genistein-faslodex (ICI 182780; 2.5 mg.kg(-1) of body weight.day(-1)). Vascular expression of eNOS, caveolin-1 and calmodulin-1 were analysed by Western blotting, eNOS activity by conversion of [(3)H]arginine into L-[(3)H]citrulline and O(2)(-) production by chemoluminescence of lucigenin. In SHRs, after 5 weeks of treatment, genistein reduced systolic blood pressure and enhanced endothelium-dependent aortic relaxation to acetylcholine, but had no effect on the vasodilator responses to sodium nitroprusside. Compared with WKY rats, SHRs had up-regulated eNOS and down-regulated caveolin-1 and calmodulin-1 expression, increased NADPH-induced O(2)(-) production, but reduced eNOS activity. Genistein increased aortic calmodulin-1 protein abundance and eNOS activity, and reduced NADPH-induced O(2)(-) production in SHRs. The pure ERalpha and ERbeta antagonist faslodex did not modify any of the changes induced by genistein in SHRs, suggesting that these effects are unrelated to ER stimulation. In conclusion, genistein reduced the elevated blood pressure and endothelial dysfunction in SHRs. This latter effect appears to be related to increased eNOS activity associated with increased calmodulin-1 expression and decreased O(2)(-) generation.

The Effects of Biological Sex and Diet on the Development of Heart Failure

“…133,134 Genistein has been shown to improve endothelial function and upregulate antioxidant genes through ERK1/2 and NFB signaling pathways, both properties that may be beneficial for cardiovascular health. 135,136 In a recent study, genistein mimicked the actions of 17␤-estradiol in its ability to localize phospho-Akt to the nucleus in cultured cardiac myocytes, a potentially cardioprotective outcome. 75 It is unclear whether the mechanism of this cardioprotection by genistein is mediated through ERs or through some other mechanism.…”

Genistein activates endothelial nitric oxide synthase in broiler pulmonary arterial endothelial cells by an Akt-dependent mechanism

“…of three independent experiments, **P ＜ 0.01 versus untreated control. studies shown that the beneficial effects of genistein were associated with the regulation on endothelial nitric oxide synthase (eNOS), because N-nitro-L-arginine methyl ester (L-NAME), the inhibitor of eNOS, abolished the restoration of endothelial function in healthy postmenopausal women (Mishra et al, 2000;Colacurci et al, 2005) and rats (Vera et al, 2007). Upon activation, eNOS produces and release endothelial nitric oxide, a crucial vasoactive molecule in maintaining vascular homeostasis because of its potent activity to relax vascular arteries, prevent intra-vasal coagulation and platelet aggregation and antagonize the proliferation of smooth muscle cells (Li and Forstermann, 2000).…”

El Consumo De Frutas Y Hortalizas Ayuda a Prevenir El Daño Endotelial

“…Los mecanismos por los cuales los flavonoides de la soya mejoran la función endotelial también incluyen la producción de NO. Por ejemplo, genisteína aumenta la expresión así como la actividad de eNOS en ratas espontáneamente hipertensas (142)(143)(144).…”