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.
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.
Authors: Folkert W Asselbergs; Scott M Williams; Patricia R Hebert; Christopher S Coffey; Hans L Hillege; Gerjan Navis; Douglas E Vaughan; Wiek H van Gilst; Jason H Moore Journal: Genomics Date: 2007-01-05 Impact factor: 5.736
Authors: Gary P Van Guilder; Mias Pretorius; James M Luther; J Brian Byrd; Kevin Hill; James V Gainer; Nancy J Brown Journal: Hypertension Date: 2008-01-07 Impact factor: 10.190