ACE Inhibition Versus Angiotensin Type 1 Receptor Antagonism: Differential Effects on PAI-1 Over Time

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 40; no. 6; pp. 859 - 865
• Main Authors: Brown, Nancy J., Kumar, Sandeep, Painter, Corrie A., Vaughan, Douglas E.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.12.2002; Hagerstown, MD Lippincott
• Subjects: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive agents; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Blood Glucose - drug effects; Blood Pressure - drug effects; Cardiovascular system; Diuretics; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide - therapeutic use; Hypertension - blood; Hypertension - drug therapy; Insulin - blood; Insulin Resistance - physiology; Losartan - therapeutic use; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Plasminogen Activator Inhibitor 1 - blood; Ramipril - therapeutic use; Receptor, Angiotensin, Type 1; Renin-Angiotensin System - drug effects; Sodium Chloride Symporter Inhibitors - therapeutic use; Tissue Plasminogen Activator - blood; Treatment Outcome; Morning; Cardiovascular disease; Ramipril; Glucose; Body mass index; Plasminogen activator inhibitor 1; Peptidyl-dipeptidase A; Losartan; Angiotensin II; angiotensin-converting enzyme; Human; Hypertension; Fasting; Enzyme; Enzyme inhibitor; Hydrochlorothiazide; Triglyceride; Insulin; plasminogen; Peptidases; Fibrin; Chemotherapy; Treatment; Biphenyl derivatives; renin; Risk factor; angiotensin; Hydrolases; Peptidyl-dipeptidases; Antihypertensive agent; Angiotensin antagonist; Thiazide; Comparative study; ACE inhibitor
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/01.hyp.0000040264.15961.48

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/m, or fasting serum triglyceride ≥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 drug×time 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.