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 journalArticlepeer-review

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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