Small artery endothelial dysfunction in postmenopausal women: in vitro function, morphology, and modification by estrogen and selective estrogen receptor modulators.
OBJECTIVE
Our objective was to assess vascular endothelial function and morphology in resistance vasculature from healthy pre- and postmenopausal women in vitro and to determine potential mechanisms of vascular protection by estrogenic compounds.


METHODS
Arteries (approximately 220 microm) were dissected from sc fat biopsies obtained from healthy premenopausal and postmenopausal women. Flow-mediated dilatation, agonist-induced endothelium-dependent and -independent relaxation, and myogenic responses to changes in intraluminal pressure were evaluated before and after incubation (3 h) with 17beta-estradiol, propyl pyrazole triol [a selective estrogen receptor-alpha (ERalpha) agonist], raloxifene (a second-generation selective ER modulator), and the phytoestrogen genistein, using pressure myography technique. In addition, endothelial morphology was assessed in arteries from pre- and postmenopausal women, and distribution of ERs within the artery wall from postmenopausal women was evaluated.


RESULTS
Functional and morphological disturbances of endothelial function were observed in small arteries from postmenopausal women. Incubation with 17beta-estradiol improved postmenopausal resistance artery function, an effect mimicked by propyl pyrazole triol but not raloxifene or genistein. Immunohistochemical staining revealed similar expression of ERalpha and ERbeta in the smooth muscle of arteries from postmenopausal women; however, ERalpha was dominant in endothelium.


CONCLUSIONS
The resistance arteries from postmenopausal women show functional and morphological abnormalities. ERalpha may contribute to vascular protection by estrogens in the peripheral resistance circulation in postmenopausal women. Selective ERalpha agonists warrant further investigation as therapeutic agents for prevention of cardiovascular disease in postmenopausal women.
Kublickiene
Karolina
K
Institution for Clinical Science, Intervention, and Technology, Department of Obstetrics and Gynecology, Karolinska Institute, Karolinska University Hospital-Huddinge Campus, 14186 Stockholm, Sweden. karolina.kublickiene@klinvet.ki.se
Svedas
Eimantas
E
Landgren
Britt-Marie
BM
Crisby
Milita
M
Nahar
Nasrin
N
Nisell
Henry
H
Poston
Lucilla
L
D000328:Adult; D001158:Arteries / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000032:analysis; D047629:Estrogen Receptor beta / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D017698:Postmenopause / Q000502:physiology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D014664:Vasodilation
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D020845:Selective Estrogen Receptor Modulators; D009599:Nitroprusside; D009569:Nitric Oxide; D004958:Estradiol; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester