title: 17Beta-estradiol increases basal but not bradykinin-stimulated release of active t-PA in young postmenopausal women.
abstract: 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 17beta-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 17beta-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 microg/min/100 mL forearm volume). 17Beta-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. 17Beta-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 17beta-estradiol. Enalaprilat potentiated bradykinin-stimulated vasodilation and t-PA antigen and activity release similarly during placebo and 17beta-estradiol treatment. 17Beta-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. 17Beta-estradiol increases basal release of active t-PA in young postmenopausal women, consistent with enhanced vascular fibrinolytic function.
authors.affiliation: Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tenn., USA. mias.pretorius@vanderbilt.edu
authors.forename: Mias
authors.initials: M
authors.lastname: Pretorius
authors.forename: Gary P
authors.initials: GP
authors.lastname: van Guilder
authors.forename: Raul J
authors.initials: RJ
authors.lastname: Guzman
authors.forename: James M
authors.initials: JM
authors.lastname: Luther
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
mesh_terms: D000367:Age Factors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D001920:Bradykinin / Q000008:administration & dosage*; D004347:Drug Interactions; D015773:Enalaprilat / Q000008:administration & dosage; D004958:Estradiol / Q000008:administration & dosage*; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D016210:Methacholine Chloride / Q000008:administration & dosage; D008875:Middle Aged; D009599:Nitroprusside / Q000008:administration & dosage; D010277:Parasympathomimetics / Q000008:administration & dosage; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017698:Postmenopause / Q000187:drug effects* / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004967:Estrogens; D010277:Parasympathomimetics; D014665:Vasodilator Agents; D016210:Methacholine Chloride; D009599:Nitroprusside; D004958:Estradiol; D007703:Peptidyl-Dipeptidase A; D010959:Tissue Plasminogen Activator; D015773:Enalaprilat; D001920:Bradykinin