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

The objectives of this study were to determine whether acute dilatory responses to estrogen receptor agonists are altered in isolated arteries from estrogen receptor beta-deficient mice (beta-ERKO) and to gain insight into the role of nitric oxide (NO) in these responses. Femoral arteries (similar to 250 mu m) from male and female beta-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 17 beta-estradiol (17 beta-E-2) and the selective estrogen receptor-alpha (ER-alpha) agonist propyl- [1H]- pyrazole- 1,3,5- triy-trisphenol (PPT) were obtained before and after NO synthase ( NOS) inhibition [N-omega-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-beta (ER-beta) agonist 2,3- bis(4-hydroxyphenyl)-propionitrile (DPN) and the contribution of NO were also assessed. Concentration-response curves to 17 beta-E-2 and PPT were similar in arteries from WT and beta-ERKO mice of both genders, but NO-mediated relaxation was different, since L-NAME reduced 17 beta-E-2 mediated relaxation in arteries from male and female beta-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 beta-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 beta-ERKO mice but differ mechanistically. Because NO appeared to contribute to responses to 17 beta-E-2 in arteries from beta-ERKO but not WT mice, the presence of ER-beta apparently inhibits ER-alpha-mediated NO relaxation.