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J Physiol Volume 551, Number 2, 721-728, September 1, 2003 DOI: 10.1113/jphysiol.2003.044107
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J Physiol (2003), 551.2, pp. 721-728
© Copyright 2003 The Physiological Society
DOI: 10.1113/jphysiol.2003.044107

Acute and chronic effects of oestrogen on endothelial tissue-type plasminogen activator release in postmenopausal women

Greta L. Hoetzer *, Brian L. Stauffer *†, Heather M. Irmiger *, Marilyn Ng *, Derek T. Smith * and Christopher A. DeSouza *‡

* Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309 and Divisions of † Cardiology and ‡ Geriatrics, Department of Medicine, University of Colorado, Health Sciences Center, Denver, CO 80262, USA

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 ~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.



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