Angiotensin-converting enzyme inhibition increases basal vascular tissue plasminogen activator release in women but not in men

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.