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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2435-2440
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume25
Issue number11
DOIs
StatePublished - Nov 2005

Keywords

  • Angiotensin
  • Inhibitors
  • Plasminogen activators
  • Women

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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