Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-beta knockout mice.
Cruz MN., Douglas G., Gustafsson JA., Poston L., Kublickiene K.
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 (approximately 250 microm) 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 17beta-estradiol (17beta-E2) 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 [Nomega-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 17beta-E2 and PPT were similar in arteries from WT and -ERKO mice of both genders, but NO-mediated relaxation was different, since L-NAME reduced 17-E2 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 17beta-E2 in arteries from beta-ERKO but not WT mice, the presence of ER- apparently inhibits ER--mediated NO relaxation.