Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-β knockout mice

Maria Natalia Cruz, Gillian Douglas, Jan Åke Gustafsson, Lucilla Poston, Karolina Kublickiene

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The objectives of this study were to determine whether acute dilatory responses to estrogen receptor agonists are altered in isolated arteries from estrogen receptor β-deficient mice (β-ERKO) and to gain insight into the role of nitric oxide (NO) in these responses. Femoral arteries (∼250 μm) from male and female β-ERKO mice and wild-type (WT) littermates (26 female, 13 in each group; and 24 male, 12 in each group) were mounted on a Multi-Myograph. Concentration-response curves to 17β-estradiol (17β-E2) and the selective estrogen receptor-α (ER-α) agonist propyl-[1H]-pyrazole-1,3,5-triy-trisphenol (PPT) were obtained before and after NO synthase (NOS) inhibition [Nω-nitro-L- arginine methyl ester (L-NAME), 0.1 mM] in arteries preconstricted with U-46619 (a thromboxane analog). In WT mice, responses to the potent estrogen receptor-β (ER-β) agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and the contribution of NO were also assessed. Concentration-response curves to 17β-E2 and PPT were similar in arteries from WT and β-ERKO mice of both genders, but NO-mediated relaxation was different, since L-NAME reduced 17β-E2 mediated relaxation in arteries from male and female β-ERKO but not WT mice (P < 0.05). NOS inhibition reduced dilation to PPT in arteries from male and female WT mice, as well as arteries from female β-ERKO mice (P < 0.05). Responses to DPN in arteries from WT female and male mice did not differ after NOS inhibition. The acute dilatory responses to estrogenic compounds are similar in WT and β-ERKO mice but differ mechanistically. Because NO appeared to contribute to responses to 17β-E2 in arteries from β-ERKO but not WT mice, the presence of ER-β apparently inhibits ER-α-mediated NO relaxation.

Original languageEnglish (US)
Pages (from-to)H823-H829
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume290
Issue number2
DOIs
StatePublished - Feb 2006

Keywords

  • Estrogen receptor knockout mice
  • Femoral arteries
  • Nitric oxide
  • Propyl-[1H]-pyrazole-1,3,5-triy-trisphenol
  • Vasodilation

ASJC Scopus subject areas

  • Physiology

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