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

Pretorius M, Luther JM, Murphey LJ, Vaughan DE, Brown NJ
Arterioscler Thromb Vasc Biol. 2005 25 (11): 2435-40

PMID: 16166566 · DOI:10.1161/01.ATV.0000186185.13977.94

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 microg/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 microg/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).

CONCLUSIONS - 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.

MeSH Terms (22)

Adult Age Factors Angiotensin-Converting Enzyme Inhibitors Blood Pressure Bradykinin Enalaprilat Female Humans Luteal Phase Male Methacholine Chloride Middle Aged Nitroprusside Parasympathomimetics Peptide Fragments Peptidyl-Dipeptidase A Postmenopause Premenopause Regional Blood Flow Sex Characteristics Tissue Plasminogen Activator Vasodilator Agents

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