Gender-specific alteration of adrenergic responses in small femoral arteries from estrogen receptor-beta knockout mice.
Estrogen receptor-beta knockout mice become hypertensive as they age, and males have a higher blood pressure than females. We hypothesized that the absence of estrogen receptor-beta may contribute to development of cardiovascular dysfunction by modification of adrenergic responsiveness in the peripheral vasculature. Small femoral arteries (internal diameter <200 microm) were isolated from estrogen receptor-beta knockout and wild-type mice and mounted on a wire myograph. Concentration-response curves to phenylephrine and norepinephrine were compared and the contribution of adrenoceptor subtypes established using specific agonists and antagonists. The involvement of endothelial factors in the modulation of resting tone was also investigated and immunohistochemical analysis used to confirm the presence or absence of estrogen receptor expression. Compared with wild type, arteries from estrogen receptor-beta knockout male, but not female, mice demonstrated gender-specific enhancement of the response to phenylephrine (alpha1-adrenoceptor agonist), which was accompanied by elevated basal tension attributable to endothelial factors. Contractile responses to the mixed adrenoceptor agonist norepinephrine did not differ significantly between estrogen receptor-beta knockout and wild type; however, beta-adrenoceptor inhibition unmasked an enhanced underlying alpha1-adrenoceptor responsiveness in estrogen receptor-beta knockout males. beta-adrenoceptor-mediated dilatation was also enhanced in estrogen receptor-beta knockout versus wild-type males. We suggest that estrogen receptor-beta modifies the adrenergic control of small artery tone in males but not in females.
Luksha
Leonid
L
Department of Obstetrics and Gynecology, Institution for Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Poston
Lucilla
L
Gustafsson
Jan-Ake
JA
Aghajanova
Lusine
L
Kublickiene
Karolina
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D047629:Estrogen Receptor beta / Q000172:deficiency / Q000502:physiology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000172:deficiency / Q000502:physiology*; D012727:Sex Characteristics; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D047629:Estrogen Receptor beta; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D015016:Yohimbine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009638:Norepinephrine