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.


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.
Pretorius
Mias
M
Veterans Affairs Medical Center, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA. mias.pretorius@vanderbilt.edu
Luther
James M
JM
Murphey
Laine J
LJ
Vaughan
Douglas E
DE
Brown
Nancy J
NJ
D000328:Adult; D000367:Age Factors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001794:Blood Pressure; D001920:Bradykinin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D015773:Enalaprilat / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008183:Luteal Phase; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D008875:Middle Aged; D009599:Nitroprusside / Q000008:administration & dosage; D010277:Parasympathomimetics / Q000008:administration & dosage; D010446:Peptide Fragments / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017698:Postmenopause; D017697:Premenopause; D012039:Regional Blood Flow / Q000187:drug effects; D012727:Sex Characteristics; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014665:Vasodilator Agents / Q000008:administration & dosage
D000806:Angiotensin-Converting Enzyme Inhibitors; D010277:Parasympathomimetics; D010446:Peptide Fragments; D014665:Vasodilator Agents; D016210:Methacholine Chloride; D009599:Nitroprusside; C079000:bradykinin (1-5); D007703:Peptidyl-Dipeptidase A; D010959:Tissue Plasminogen Activator; D015773:Enalaprilat; D001920:Bradykinin