TY - JOUR
T1 - Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II
T2 - Evidence of a potential interaction between the renin-angiotensin system and fibrinolytic function
AU - Ridker, Paul M.
AU - Gaboury, Cynthia L.
AU - Conlin, Paul R.
AU - Seely, Ellen W.
AU - Williams, Gordon H.
AU - Vaughan, Douglas E.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1993/6
Y1 - 1993/6
N2 - 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.
AB - 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.
KW - Angiotensin
KW - Fibrinolysis
KW - Plasminogen activator inhibitor-1
KW - Thrombosis
KW - Tissue-type plasminogen activator
UR - http://www.scopus.com/inward/record.url?scp=0027267328&partnerID=8YFLogxK
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M3 - Article
C2 - 8504511
AN - SCOPUS:0027267328
SN - 0009-7322
VL - 87
SP - 1969
EP - 1973
JO - Circulation
JF - Circulation
IS - 6
ER -