Dietary soy isoflavone‐induced increases in antioxidant and eNOS gene expression lead to improved endothelial function and reduced blood pressure in vivo

Abstract

Epidemiological evidence suggests that populations consuming large amounts of soy protein have a reduced incidence of coronary heart disease (1–5). The cardiovascular risks associated with conventional hormone replacement therapy in postmenopausal women (5–7) have precipitated a search for alternative estrogen receptor modulators. Here we report that long‐term feeding of rats with a soy protein‐rich (SP) diet during gestation and adult life results in decreased oxidative stress, improved endothelial function, and reduced blood pressure in vivo measured by radiotelemetry in aged male offspring. Improved vascular reactivity in animals fed an SP diet was paralleled by increased mitochondrial glutathione and mRNA levels for endothelial nitric oxide synthase (eNOS) and the antioxidant enzymes manganese superoxide dismutase and cytochrome c oxidase. Reduced eNOS and antioxidant gene expression, impaired endothelial function, and elevated blood pressure in animals fed a soy‐deficient diet was reversed after refeeding them an SP diet for 6 months. Our findings suggest that an SP diet increases eNOS and antioxidant gene expression in the vasculature and other tissues, resulting in reduced oxidative stress and increased NO bioavailability. The improvement in endothelial function, increased gene expression, and reduced blood pressure by soy isoflavones have implications for alternative therapy for postmenopausal women and patients at risk of coronary heart disease.

Genistein Induces Estrogen-Like Effects in Ovariectomized Rats but Fails to Increase Cardiac GLUT4 and Oxidative Stress

“…23 Cellular defenses against oxidative stress also include superoxide dismutase, catalase, and glutathione peroxidase, all of which are increased with either estrogen or genistein. 11,45,46 In conclusion, the results of this study demonstrate favorable effects of genistein on physical characteristics in the OVX rat, used here as a model for the postmenopausal condition. These favorable effects are evidenced by increased uterine weight and femur weight, along with reduced heart rate and pulse pressure.…”

“…8 One of the more notable cardiovascular-related effects of genistein is a lowering of blood pressure observed in both hypertensive and normotensive postmenopausal women 9,10 or rat models. 11 This beneficial effect is purported to be mediated via improvements in endothelial function and reductions in both antioxidant stress in aorta and arterial stiffness. 12 Moreover, genistein treatment in postmenopausal women was shown to increase flow-mediated endothelium vasodilation, likely by increasing the nitric oxide to endothelin ratio, 11,[13][14][15] and has a beneficial effect on the lipid profile.…”

“…11 This beneficial effect is purported to be mediated via improvements in endothelial function and reductions in both antioxidant stress in aorta and arterial stiffness. 12 Moreover, genistein treatment in postmenopausal women was shown to increase flow-mediated endothelium vasodilation, likely by increasing the nitric oxide to endothelin ratio, 11,[13][14][15] and has a beneficial effect on the lipid profile. 16 As genistein is pleiotropic in nature, genistein therapy has been associated with improved bone health in postmenopausal women and ovariectomized (OVX) mice.…”

“…31 Mahn et al 11 showed that male rats fed a soy-enriched diet for up to 10 months had significantly lowered systolic and diastolic blood pressures. Similarly, Li et al 32 showed that genistein treatment (0.4 mg=kg=day for 21 days) decreased mean arterial pressure in OVX rats.…”

The Effects of Cirsium japonicum on Lipid Profile in Ovariectomized Rats

“…The U.S. Food and Drug Administration has endorsed the benefits of soy-based food products in lowering arterial blood pressure and oxidative stress in human subjects with mild to moderate hypertension (Hodgson et al, 1999;Rivas et al, 2002). In addition, a recent report showed that dietary soy protein leads to increased antioxidant, endothelial nitric oxide synthase gene expression and protected cancers, resulting in improved endothelial function in vitro, and reduced blood pressure in vivo in aging male rats (Mahn et al, 2005). Chinese traditional medicine has become increasingly popular and widely used over recent years.…”