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Cardiovascular Research 2003 57(1):186-194; doi:10.1016/S0008-6363(02)00655-7
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Genistein supplementation stimulates the oxytocin system in the aorta of ovariectomized rats

Donghao Wanga, Jolanta Gutkowskaa,c, Mieczyslaw Marcinkiewiczb, Grazyna Rachelskaa and Marek Jankowskia,c,*

aLaboratory of Cardiovascular Biochemistry, Centre Hospitalier de l’Université de Montréal–Hôtel-Dieu, 3850 St. Urbain Street, Masson Pavilion, Montreal, Quebec, Canada H2W 1T7
bCytochem, Montreal, Quebec, Canada
cDepartment of Medicine, Université de Montréal, Montreal, Quebec, Canada

* Corresponding author. Tel.: +1-514-890-8000x12757; fax: +1-514-412-7199. marek.jankowski{at}umontreal.ca

Objective: In the present study, we localized oxytocin (OT) and its receptor (OTR) in the rat aorta, and investigated whether genistein, an isoflavonic phytoestrogen, influences their expression in ovariectomized (OVX) rats deficient in estrogen. Methods and results: OVX Sprague–Dawley rats were randomized to the following groups: genistein (from 0.02 to 5 µg/g/day, s.c. for 10 days), estradiol (E2, 0.1 µg/g/day, s.c. for 10 days) or their respective vehicles. OT and OTR immunostaining was concentrated in the aortic tunica intima, suggesting their paracrine/autocrine action within endothelial cells. Reverse transcription-polymerase chain reaction analysis showed that 1 and 5 µg/g but not 0.1 µg/g genistein elevated OT mRNA (2-fold P<0.05), OTR mRNA (2.5-fold, P<0.05) and endothelial nitric oxide synthase (eNOS) mRNA (2-fold, P<0.05) in the aorta of OVX rats. In addition, genistein treatment increased estrogen receptor {alpha} (ER{alpha}) (2- to 3-fold, P<0.05) but resulted in a 50% decrease of ERβ (P<0.05). These genistein effects were neutralized by treatment of OVX rats with the ER antagonist ICI 182,780 (1.5 µg/g/day, s.c. for 10 days). Similarly, Western blot analysis revealed an increase of 67-kDa OTR, 140-kDa eNOS, 62-kDa ER{alpha} and a decrease of 55-kDa ERβ (P<0.05) in the aorta of OVX rats treated with genistein. In contrast, the treatment of OVX rats with E2 elevated ERβ mRNA (1.5 fold, P<0.05) but similarly to genistein increased OT, OTR, eNOS and ER{alpha} mRNA. Conclusion: These results provide the first evidence of OT and OTR co-localization in endothelial cells. The response to genistein via ER activation can be regarded as a recovery from endothelial dysfunction induced by ovariectomy.

KEYWORDS Endothelial function; Gene expression; Hormones; Receptors; Vasoconstriction/dilation


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