17β-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women

Angiotensin-converting enzyme inhibition potentiates basal and bradykinin-stimulated tissue-type plasminogen activator (t-PA) release to a greater extent in women than in men. This study tested the hypothesis that 17β-estradiol enhances the effect of angiotensin-converting enzyme inhibition on t-PA release in young postmenopausal women. We conducted a double-blind, prospective, crossover study in 14 young postmenopausal women (mean age 48.2±2.3 years) who were randomized to receive 17β-estradiol (1 mg/d) or matching placebo for 4 weeks. At the end of each treatment period, we measured the effect of intraarterial infusion of bradykinin, methacholine, and nitroprusside on forearm blood flow and net t-PA release, before and during intraarterial enalaprilat (0.33 μg/min/100 mL forearm volume). 17β-estradiol significantly reduced baseline venous plasminogen activator inhibitor-1 antigen (4.4±1.4 versus 10.4±2.5 ng/mL, P =0.001) and t-PA antigen (5.5±0.6 versus 7.5±1.3 ng/mL, P =0.022) compared with placebo. 17β-estradiol increased basal forearm vascular release of active t-PA compared with placebo (1.2±0.3 IU/mL/min versus 0.4±0.1 IU/mL/min respectively, P =0.032), without increasing t-PA antigen release ( P =0.761). Enalaprilat significantly increased basal net t-PA antigen release (from −0.8±1.0 to 3.2±1.2 ng/min/100 mL, P =0.012), but not the release of active t-PA, during either placebo or 17β-estradiol. Enalaprilat potentiated bradykinin-stimulated vasodilation and t-PA antigen and activity release similarly during placebo and 17β-estradiol treatment. 17β-estradiol treatment does not alter the effect of angiotensin-converting enzyme inhibition on basal t-PA antigen or on bradykinin-stimulated t-PA antigen or activity release. 17β-estradiol increases basal release of active t-PA in young postmenopausal women, consistent with enhanced vascular fibrinolytic function.