Chronic administration of genistein improves endothelial dysfunction in spontaneously hypertensive rats: involvement of eNOS, caveolin and calmodulin expression and NADPH oxidase activity
Résumé
The soy derived phytoestrogen genistein has been suggested to be protective in cardiovascular diseases. We have analyzed if chronic oral genistein might influence the endothelial function in male spontaneously hypertensive rats (SHR) via estrogen receptors (ERs), changes in endothelial NO synthase (eNOS) activity and vascular superoxide (O 2} -}) production. Rats (23 week old) were divided into the following groups, Wistar Kyoto (WKY)-vehicle; SHR-vehicle; WKY-genistein (10 mg/kg/day); SHR-genistein; SHR-genistein-faslodex (ICI 182780, 2.5 mg/kg/day). Vascular expression of endothelial NO synthase (eNOS), caveolin-1 and calmodulin-1 were analyzed by western blot, eNOS activity by conversion of [ 3}H]arginine to L-[ 3}H]citrulline and O 2} -} production by chemoluminescence of lucigenin. In SHR, after 5 weeks of treatment, genistein reduced systolic blood pressure, enhanced the endothelium-dependent aortic relaxation to acetylcholine, but had no effect on the vasodilator responses to sodium nitroprusside. Compared to WKY, SHR showed upregulated eNOS and downregulated 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 SHR. The pure {alpha} and {beta} estrogenic receptor antagonist faslodex did not modify any changes induced by genistein in SHR, suggesting that these effects are unrelated to ERs stimulation. In conclusion, genistein reduced the elevated blood pressure and the endothelial dysfunction in SHR. This latter effect seems to be related to the increased eNOS activity, associated with increased calmodulin-1 expression, and the decreased O 2} -} generation.
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