on October 28, 2002
Published online before print October 28, 2002, doi: 10.1161/01.HYP.0000040264.15961.48
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Submitted on May 1, 2002
From the Divisions of Clinical Pharmacology, Department of Pharmacology (N.J.B., S.K.), and Cardiovascular Medicine, Department of Medicine (C.A.P.), Vanderbilt University Medical Center, Nashville; and the Veteran's Administration Medical Center (D.E.V.), Nashville, Tenn. * To whom correspondence should be addressed. E-mail: nancy.brown{at}mcmail.vanderbilt.edu..
Abstract—ACE inhibition reduces plasminogen activator inhibitor-1 (PAI-1), a risk factor for myocardial infarction, whereas the effect of angiotensin receptor antagonism on PAI-1 is uncertain. The present study compares the time course of effects of ACE inhibition and angiotensin type 1 (AT1) receptor antagonism on morning plasma PAI-1 antigen. Blood pressure and endocrine, metabolic, and fibrinolytic variables were measured in 20 insulin-resistant (defined by fasting glucose >8.3 mmol/L, body mass index >28 kg/m2, or fasting serum triglyceride
Revised on May 24, 2002
ACE Inhibition Versus Angiotensin Type 1 Receptor Antagonism. Differential Effects on PAI-1 Over Time
Nancy J. Brown*;
2.8 mmol/L) hypertensive subjects (mean age, 47.9±2.1 years) (1) before and after 1 week of hydrochlorothiazide 12.5 mg/d, and (2) before and 1, 3, 4, and 6 weeks after addition of ramipril (escalated to 10 mg/d) or losartan (escalated to 100 mg/d). Hydrochlorothiazide decreased systolic (P=0.011) and diastolic (P=0.019) pressure. Ramipril (from 133.6±5.1/94.5±2.4 to 127.0±3.1/91.4±3.3 mm Hg) or losartan (from 137.0±3.9/93.1±2.9 to 123.7±2.6/86.4±2.1 mm Hg) further reduced systolic (P=0.009) and diastolic (P=0.037) pressure. The pressure effects of the 2 drugs were similar. Hydrochlorothiazide increased plasma PAI-1 (P=0.013) but not tissue-type plasminogen activator (tPA) (P=0.431) antigen. Addition of either ramipril or losartan significantly decreased plasma PAI-1 antigen (P=0.046). However, the effect of losartan on PAI-1 antigen was not sustained throughout the 6-week treatment period, such that there was a significant drugxtime interaction (P=0.043). tPA antigen decreased during either ramipril or losartan (P=0.032), but tPA activity decreased only during losartan (P=0.018). Short-term interruption of the renin-angiotensin-aldosterone system by either ACE inhibition or AT1 receptor antagonism decreases PAI-1 antigen, but the duration of this effect is greater for ACE inhibition than for AT1 receptor antagonism.
Key words: fibrin • plasminogen • angiotensin • renin • angiotensin-converting enzyme
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