This Article Free upon publication Full Text Full Text (PDF) Data Supplement All Versions of this Article: 51/4/1190    most recent HYPERTENSIONAHA.107.105627v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pretorius, M. Articles by Brown, N. J. Search for Related Content PubMed PubMed Citation Articles by Pretorius, M. Articles by Brown, N. J. Related Collections Fibrinolysis Other Vascular biology

(Hypertension. 2008;51:1190.)
© 2008 American Heart Association, Inc.

Go Red Original Articles

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

Mias Pretorius; Gary P. van Guilder; Raul J. Guzman; James M. Luther; Nancy J. Brown

From the Department of Anesthesiology (M.P.), Division of Vascular Surgery (R.J.G.), Department of Surgery, Division of Clinical Pharmacology (M.P., G.P.v.G., J.M.L., N.J.B.), Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn.

Correspondence to Mias Pretorius, MBChB, MSc, 560 RRB, Vanderbilt University Medical Center, Nashville, TN 37232-6602. E-mail mias.pretorius{at}vanderbilt.edu

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.

Key Words: estradiol • angiotensin-converting enzyme inhibition • postmenopausal women • plasminogen activator • bradykinin