Published Online
on October 10, 2005

A more recent version of this article appeared on November 1, 2005

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Submitted on June 17, 2005
Revised on July 8, 2005

Gender-Specific Alteration of Adrenergic Responses in Small Femoral Arteries From Estrogen Receptor- Knockout Mice

Leonid Luksha; Lucilla Poston; Jan-Åke Gustafsson; Lusine Aghajanova; and Karolina Kublickiene^*

From the Departments of Obstetrics and Gynecology (L.L., L.A., K.K.) and Medical Nutrition (L.P.), Institution for Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Huddinge Campus, Stockholm, Sweden; and Maternal and Fetal Research Unit (J.-Å.G.), St Thomas’s Hospital, Kings College London, United Kingdom.

^* To whom correspondence should be addressed. E-mail: karolina.kublickiene{at}klinvet.ki.se.

Abstract--Estrogen receptor- knockout mice become hypertensive as they age, and males have a higher blood pressure than females. We hypothesized that the absence of estrogen receptor- may contribute to development of cardiovascular dysfunction by modification of adrenergic responsiveness in the peripheral vasculature. Small femoral arteries (internal diameter <200 µm) were isolated from estrogen receptor- knockout and wild-type mice and mounted on a wire myograph. Concentration-response curves to phenylephrine and norepinephrine were compared and the contribution of adrenoceptor subtypes established using specific agonists and antagonists. The involvement of endothelial factors in the modulation of resting tone was also investigated and immunohistochemical analysis used to confirm the presence or absence of estrogen receptor expression. Compared with wild type, arteries from estrogen receptor- knockout male, but not female, mice demonstrated gender-specific enhancement of the response to phenylephrine (₁-adrenoceptor agonist), which was accompanied by elevated basal tension attributable to endothelial factors. Contractile responses to the mixed adrenoceptor agonist norepinephrine did not differ significantly between estrogen receptor- knockout and wild type; however, -adrenoceptor inhibition unmasked an enhanced underlying ₁-adrenoceptor responsiveness in estrogen receptor- knockout males. -adrenoceptor-mediated dilatation was also enhanced in estrogen receptor- knockout versus wild-type males. We suggest that estrogen receptor- modifies the adrenergic control of small artery tone in males but not in females.

Key words: gender • endothelium • estrogen • arteries • vasoconstriction • adrenergic receptor agonists

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