Abstract
Isoflavones, such as daidzein, are proposed to possess vasculoprotective properties, perhaps through a mechanism similar to estrogen. Our experiments aimed to test the hypothesis that daidzein and 17 beta-estradiol enhance endothelium-dependent relaxation through an increase in NO synthesis due to an increase in activity or expression of endothelial nitric oxide synthase (eNOS). Male rats were treated with daidzein (0.2 mg/kg per day sc), 17 beta-estradiol (0.1 mg/kg per day sc), or vehicle for 7 days and reactivity of isolated aortic rings was then determined. ACh-induced relaxation was significantly enhanced in aortic rings from rats treated with daidzein or 17 beta-estradiol but the relaxant responses to the endothelium-independent dilators sodium nitroprusside or isoprenaline were not different. Nitrite production and the level of cGMP were significantly greater in aortae from daidzein and 17 beta-estradiol compared with vehicle-treated rats. Daidzein and 17 beta-estradiol did not alter eNOS protein in endothelium-intact aortae but reduced expression of caveolin-1 and increased expression of calmodulin, changes that would account for an increase in eNOS activity. There were no differences between groups in the expression of calmodulin and caveolin-1 in arteries when the endothelium was removed. Daidzein or 17 beta-estradiol treatment selectively enhances endothelium-dependent relaxation in male rats through an increase in eNOS activity. The increase in eNOS activity is associated with a decreased expression of caveolin-1 and an increased expression of calmodulin in endothelial cells.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / pharmacology
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Animals
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Aorta / cytology
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Aorta / drug effects
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Aorta / metabolism
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Body Weight / drug effects
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Calmodulin / genetics
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Calmodulin / metabolism*
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Caveolin 1
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Caveolins / antagonists & inhibitors
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Caveolins / genetics
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Caveolins / metabolism*
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Cyclic GMP / chemistry
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Cyclic GMP / metabolism
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Drug Synergism
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Endothelium, Vascular / metabolism
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Endothelium, Vascular / pathology
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Estradiol / administration & dosage
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Estradiol / analogs & derivatives*
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Estradiol / pharmacokinetics*
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Estradiol / pharmacology
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Fulvestrant
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Gene Expression / drug effects
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Gene Expression / physiology
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Injections, Subcutaneous
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Isoflavones / administration & dosage
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Isoflavones / pharmacokinetics*
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Isoproterenol / pharmacology
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Male
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Muscle Contraction / drug effects
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Muscle Relaxation / drug effects
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Muscle, Smooth, Vascular / drug effects
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Nitric Oxide / biosynthesis
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Nitric Oxide / genetics
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / chemistry
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase / metabolism*
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Nitric Oxide Synthase Type III
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Nitroarginine / pharmacology
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Nitroprusside / pharmacology
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Organ Size / drug effects
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Phenoxybenzamine / pharmacology
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Rats
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Rats, Sprague-Dawley
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Testis / anatomy & histology
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Testis / drug effects
Substances
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Calmodulin
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Cav1 protein, rat
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Caveolin 1
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Caveolins
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Isoflavones
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Phenoxybenzamine
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Nitroprusside
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Nitroarginine
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Fulvestrant
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Nitric Oxide
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Estradiol
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daidzein
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type III
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Nos3 protein, rat
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Cyclic GMP
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Isoproterenol
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Acetylcholine