Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-beta 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 (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.
Cruz
Maria Natalia
MN
Institution for Clinical Science, Intervention, and Technology, Division of Obstetrics and Gynecology, Karolinska Institutet, Huddinge, 14186 Stockholm, Sweden.
Douglas
Gillian
G
Gustafsson
Jan-Ake
JA
Poston
Lucilla
L
Kublickiene
Karolina
K
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists; D047629:Estrogen Receptor beta / Q000819:agonists / Q000172:deficiency*; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000494:pharmacology; D009994:Osmolar Concentration; D010636:Phenols / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012727:Sex Characteristics; D014664:Vasodilation / Q000187:drug effects; D011422:Propionates
D004791:Enzyme Inhibitors; D004958:Estradiol; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D009570:Nitriles; D010636:Phenols; D011720:Pyrazoles; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol