title: Acute and chronic effects of oestrogen on endothelial tissue-type plasminogen activator release in postmenopausal women.
abstract: The capacity of vascular endothelium to locally release tissue-type plasminogen activator (t-PA) represents an important endogenous defence mechanism against intravascular fibrin deposition and thrombosis. We determined the influence of chronic and acute oestrogen administration on endothelial t-PA release in postmenopausal women. Sixty-three healthy postmenopausal women were studied: 31 non-users (age 58 +/- 1 years) and 32 users of hormone replacement therapy, including oestrogen alone (ORT: 62 +/- 2 years; n = 15) and in combination with progesterone (HRT: 57 +/- 1 years; n = 17). Net endothelial t-PA release was determined in vivo, in response to intrabrachial infusions of bradykinin and sodium nitroprusside. To examine the acute effects of oestrogen on endothelial t-PA release, bradykinin and sodium nitroprusside dose-response curves were repeated in the presence of 17 beta-oestradiol in 20 of the 31 non-users. Net endothelial release of t-PA was ~30 % higher (P < 0.01) in women taking ORT (from 2.0 +/- 1.0 to 83.6 +/- 9.2 ng (100 ml tissue)-1 min-1) compared with those taking HRT (from 1.4 +/- 0.4 to 63.5 +/- 5.6 ng (100 ml tissue)-1 min-1) and those not taking supplementation (1.0 +/- 0.7 to 63.0 +/- 4.7 ng (100 ml tissue)-1 min-1). Intra-arterial infusion of 17 beta-oestradiol significantly potentiated bradykinin-induced t-PA release. Net endothelial release of t-PA was approximately 45 % higher (P < 0.01) after (from 1.0 +/- 0.8 to 87.4 +/- 9.9 ng (100 ml tissue)-1 min-1) versus before (1.2 +/- 0.6 to 60.8 +/- 5.6 ng (100 ml tissue)-1 min-1) acute 17 beta-oestradiol administration. Our results suggest that oestrogen has a direct modulatory effect on the capacity of the endothelium to release t-PA in healthy postmenopausal women. However, progesterone appears to oppose the favourable influence of oestrogen on endothelial fibrinolytic capacity.
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Greta L
authors.initials: GL
authors.lastname: Hoetzer
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
authors.forename: Heather M
authors.initials: HM
authors.lastname: Irmiger
authors.forename: Marilyn
authors.initials: M
authors.lastname: Ng
authors.forename: Derek T
authors.initials: DT
authors.lastname: Smith
authors.forename: Christopher A
authors.initials: CA
authors.lastname: DeSouza
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D004727:Endothelium / Q000378:metabolism*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D017698:Postmenopause / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D004967:Estrogens; D008055:Lipids; D009599:Nitroprusside; D011374:Progesterone; D010959:Tissue Plasminogen Activator; D001920:Bradykinin