Circulation, Vol 87, 1969-1973, Copyright © 1993 by American Heart Association
PM Ridker, CL Gaboury, PR Conlin, EW Seely, GH Williams and DE Vaughan
BACKGROUND. Recent clinical trial data indicate that the use of angiotensin
converting enzyme (ACE) inhibitors among patients with left ventricular
dysfunction results in reduced rates of coronary thrombosis, a provocative
finding that suggests a potential interaction between the renin-angiotensin
system and fibrinolytic function. METHODS AND RESULTS. In four normotensive
subjects and six hypertensive patients, we investigated whether infusion of
angiotensin II (Ang II) affected circulating levels of plasminogen
activator inhibitor-1 (PAI- 1), the most important physiological inhibitor
of tissue-type plasminogen activator (t-PA). Overall, mean levels of PAI-1
antigen increased significantly from 20.1 ng/mL before Ang II infusion to
36.0 ng/mL at the end of Ang II infusion (p = 0.008), whereas no change in
PAI-1 was observed for control subjects infused with 5% dextrose (p =
0.46). Among the normotensive subjects for whom graded doses of Ang II were
infused at 0, 1, 3, and 10 ng.kg-1.min-1, mean PAI-1 levels increased
sequentially from 14.7 ng/mL to 23.0, 26.8, and 33.5 ng/mL, a dose-response
relation that, compared with controls, was highly significant (p <
0.001). Among the hypertensive patients for whom a single 45-minute
infusion of Ang II was given at a dose of 3 ng.kg- 1.min-1, PAI-1 levels
increased from 23.7 to 37.7 ng/mL, whereas PAI-1 levels among control
subjects infused with 5% dextrose decreased from 16.9 to 10.8 ng/mL (p =
0.04). Finally, when compared with infusion of 5% dextrose solution,
infusion of Ang II appeared to have little effect on circulating levels of
t-PA antigen. CONCLUSIONS. These in vivo data suggest that infusion of Ang
II results in a rapid increase in circulating levels of PAI-1, a finding
that may help to explain clinical observations linking the
renin-angiotensin system and thrombotic risk.
ARTICLES
Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II. Evidence of a potential interaction between the renin- angiotensin system and fibrinolytic function
Divisions of Cardiology, Brigham and Women's Hospital, Boston, MA 02115.
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