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Research ArticleCARDIOVASCULAR

Effect of Short-Term Phytoestrogen Treatment in Male Rats on Nitric Oxide-Mediated Responses of Carotid and Cerebral Arteries: Comparison with 17β-Estradiol

Christopher G. Sobey, Jane M. Weiler, Mirna Boujaoude and Owen L. Woodman
Journal of Pharmacology and Experimental Therapeutics July 2004, 310 (1) 135-140; DOI: https://doi.org/10.1124/jpet.103.063255
Christopher G. Sobey
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Jane M. Weiler
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Mirna Boujaoude
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Owen L. Woodman
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Abstract

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, 17β-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 17β-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 17β-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 17β-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 17β-estradiol-treated rats. eNOS expression was unaffected by the treatments. These data suggest that short-term administration of daidzein or 17β-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.

Footnotes

  • This work was supported by a project grant from the National Health and Medical Research Council of Australia. C.G.S. is supported by National Health and Medical Research Council R. D. Wright Career Development Award 209160.

  • DOI: 10.1124/jpet.103.063255.

  • ABBREVIATIONS: eNOS, endothelial nitric-oxide synthase; NO, nitric oxide; HRT, hormone replacement therapy; KPSS, high K+-containing physiological saline solution; PBZ, phenoxybenzamine; NOx, nitrite + nitrate; l-NNA, NG-nitro-l-arginine; PBS, phosphate-buffered saline; mAb, monoclonal antibody; ANOVA, analysis of variance.

    • Received November 12, 2003.
    • Accepted March 29, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 310 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 310, Issue 1
1 Jul 2004
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Research ArticleCARDIOVASCULAR

Effect of Short-Term Phytoestrogen Treatment in Male Rats on Nitric Oxide-Mediated Responses of Carotid and Cerebral Arteries: Comparison with 17β-Estradiol

Christopher G. Sobey, Jane M. Weiler, Mirna Boujaoude and Owen L. Woodman
Journal of Pharmacology and Experimental Therapeutics July 1, 2004, 310 (1) 135-140; DOI: https://doi.org/10.1124/jpet.103.063255

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Research ArticleCARDIOVASCULAR

Effect of Short-Term Phytoestrogen Treatment in Male Rats on Nitric Oxide-Mediated Responses of Carotid and Cerebral Arteries: Comparison with 17β-Estradiol

Christopher G. Sobey, Jane M. Weiler, Mirna Boujaoude and Owen L. Woodman
Journal of Pharmacology and Experimental Therapeutics July 1, 2004, 310 (1) 135-140; DOI: https://doi.org/10.1124/jpet.103.063255
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