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 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.