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 O2− (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 [3H]arginine into L-[3H]citrulline and O2− 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 O2− production, but reduced eNOS activity. Genistein increased aortic calmodulin-1 protein abundance and eNOS activity, and reduced NADPH-induced O2− production in SHRs. The pure ERα and ERβ 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 O2− generation.
Chronic administration of genistein improves endothelial dysfunction in spontaneously hypertensive rats: involvement of eNOS, caveolin and calmodulin expression and NADPH oxidase activity
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Rocio Vera, Manuel Sánchez, Milagros Galisteo, Inmaculada Concepcion Villar, Rosario Jimenez, Antonio Zarzuelo, Francisco Pérez-Vizcaíno, Juan Duarte; Chronic administration of genistein improves endothelial dysfunction in spontaneously hypertensive rats: involvement of eNOS, caveolin and calmodulin expression and NADPH oxidase activity. Clin Sci (Lond) 1 February 2007; 112 (3): 183–191. doi: https://doi.org/10.1042/CS20060185
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