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CARDIOVASCULAR
-Estradiol
Department of Pharmacology, the University of Melbourne, Parkville, Victoria, Australia
The use of estrogen for protection against vascular dysfunction is limited due to its effects on the reproductive system, particularly in males. We postulated that daidzein, an isoflavone with estrogen-like effects on the systemic vasculature but not the reproductive system, might enhance nitric oxide (NO)-mediated cerebral vasodilatation. Male rats were administered vehicle, 17
-estradiol (0.1 mg/kg s.c.), or daidzein (0.2 mg/kg s.c.) daily for 7 days. Basal and acetylcholine-stimulated NO release was assessed in vitro via carotid arterial rings or in vivo by measuring changes in basilar artery diameter. Levels of protein expression of endothelial NO synthase (eNOS), caveolin-1, and calmodulin were assessed in carotid arteries using Western analysis. Plasma NO levels were doubled by daidzein or 17
-estradiol. NO production and endothelium-dependent contraction in response to the NOS inhibitor NG-nitro-L-arginine (L-NNA; 100 µM) was enhanced by 50 to 100% in carotid arteries from rats treated with daidzein or 17
-estradiol. Acetylcholine-induced relaxation was selectively enhanced in carotid arteries from rats treated with daidzein. Similarly, constrictor responses of the basilar artery to L-NNA in vivo were selectively augmented by
100% by 17
-estradiol treatment and tended to be
50% greater in daidzein-treated rats. Expression of caveolin-1 was decreased, and calmodulin was increased, in vessels from daidzein- or 17
-estradiol-treated rats. eNOS expression was unaffected by the treatments. These data suggest that short-term administration of daidzein or 17
-estradiol modulates cerebral artery reactivity in males by enhancing synthesis and release of endothelium-derived NO. Isoflavone therapy may therefore be a feasible approach to protect against cerebrovascular disease and stroke.
Address correspondence to: Dr. Christopher G. Sobey, Department of Pharmacology, The University of Melbourne, Grattan St., Parkville, Victoria 3010, Australia. E-mail: cgsobey{at}unimelb.edu.au
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