Endogenous NO Regulates Plasminogen Activator Inhibitor-1 During Angiotensin-Converting Enzyme Inhibition

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2006-03, Vol.47 (3), p.441-448
• Main Authors: Brown, Nancy J, Muldowney, James A.S, Vaughan, Douglas E
• Format: Article
• Language: English
• Subjects: Adult; Aldosterone - metabolism; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Antihypertensive agents; Arginine - pharmacology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Double-Blind Method; Drug Combinations; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Female; Fibrinolysis - drug effects; Hemodynamics - drug effects; Humans; Infusions, Intravenous; Male; Medical sciences; Middle Aged; NG-Nitroarginine Methyl Ester - administration & dosage; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - metabolism; Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Pharmacology. Drug treatments; Plasminogen Activator Inhibitor 1 - blood; Prodrugs - pharmacology; Ramipril - pharmacology; Reference Values; Renin-Angiotensin System - drug effects
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000202478.79587.1a

To test the hypothesis that NO contributes to effects of angiotensin-converting enzyme inhibitors on fibrinolysis, fibrinolytic balance was assessed in 17 normal subjects during placebo and after randomized, double-blind 4-week treatment with the NO precursor l-arginine (3 g TID), ramipril (10 mg QD), or l-arginine+ramipril. Neither l-arginine nor ramipril alone affected basal plasminogen activator inhibitor-1 or tissue-type plasminogen activator (t-PA) antigen in these salt-replete subjects in whom plasma renin activity was suppressed (mean±SD 0.7±0.5 ng angiotensin I/mL per hour). In contrast, l-arginine+ramipril reduced morning plasminogen activator inhibitor-1 antigen (10.8±9.5 ng/mL) and the molar ratio of plasminogen activator inhibitor-1:t-PA (2.3±1.6) compared with placebo (13.5±10.8 ng/mL, P=0.006; ratio 2.9±2.1, P=0.015) or ramipril alone (15.2±13.2 ng/mL, P=0.009; ratio 3.7±3.3, P=0.005). l-arginine and ramipril synergistically increased d-dimers (23.1±31.5, 29.7±50.0, 35.1±50.0, and 57.1±144.8 ng/mL during placebo, l-arginine, ramipril, and l-arginine+ramipril, respectively; P