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

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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 β‐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 β‐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 β‐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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