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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2435.)
© 2005 American Heart Association, Inc.

Thrombosis

Angiotensin-Converting Enzyme Inhibition Increases Basal Vascular Tissue Plasminogen Activator Release in Women But Not in Men

Mias Pretorius; James M. Luther; Laine J. Murphey; Douglas E. Vaughan; Nancy J. Brown

From Veterans Affairs Medical Center (M.P., D.E.V.), Department of Anesthesiology (M.P.), the Divisions of Clinical Pharmacology (J.M.L., L.J.M., N.J.B.) and Cardiovascular Medicine (D.E.V.), Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn.

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

Objective— Angiotensin-converting enzyme inhibition (ACEI) increases vascular tissue plasminogen activator (t-PA) release through endogenous bradykinin (BK). We tested the hypothesis that gender influences the effect of ACEI on t-PA release.

Methods and Results— We measured the effect of intra-arterial enalaprilat (0.33 µg/min per 100 mL forearm volume) on forearm blood flow (FBF) and net t-PA release before and during BK (25 to 400 ng/min) and methacholine (3.2 to 12.8 µg/min) in premenopausal women, postmenopausal women not using hormone replacement, young men, and older men. Baseline net t-PA release was similar among groups. Enalaprilat increased basal t-PA release in premenopausal (from 0.9±1.0 to 5.1±1.7 ng/min per 100 mL, P=0.023) and postmenopausal women (from –3.9±2.2 to 3.9±1.1 ng/min per 100 mL, P=0.010) but not in young or older men (P=0.028 men versus women). Enalaprilat potentiated the effect of exogenous BK on FBF similarly in all groups. However, during enalaprilat, BK-stimulated t-PA release was greatest in premenopausal women (339.9±86.4 ng/min per 100 mL at the 100 ng/min dose, P<0.05 versus any other group), intermediate in postmenopausal women (243.8±51.1 ng/min per 100 mL, P<0.05 versus either male group), and least in young (111.9±19.2 ng/min/100 mL) and older men (103.4±27.6 ng/min/100 mL).

Conclusion— ACEI enhances basal t-PA release in women, independent of menopausal status, but not in men. During ACEI, both gender and menopausal status affect BK stimulated t-PA release.

This study tests the hypothesis that gender influences the effect of ACE inhibition on vascular t-PA release. Enalaprilat increased basal t-PA release in premenopausal (P=0.023) and postmenopausal women (P=0.010) but not in young or older men. During enalaprilat, basal t-PA release was significantly greater in women compared with men (P=0.028).

Key Words: angiotensin • inhibitors • plasminogen activators • women

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