Effect of Sulfhydryl and non-Sulfhydryl Angiotensin-Converting Enzyme Inhibitors on Endothelial Function in Essential Hypertensive Patients

• Published in: American journal of hypertension Vol. 20; no. 4; pp. 443 - 450
• Main Authors: Pasini, Anna Fratta, Garbin, Ulisse, Nava, Maria Cristina, Stranieri, Chiara, Pellegrini, Michele, Boccioletti, Veronica, Luchetta, Maria Laura, Fabrizzi, Paolo, Lo Cascio, Vincenzo, Cominacini, Luciano
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-04-2007; Oxford University Press; Elsevier Science
• Subjects: ACE inhibitor; adhesion molecules; Adrenergic beta-Antagonists - pharmacology; Adrenergic beta-Antagonists - therapeutic use; Adult; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive agents; Arterial hypertension. Arterial hypotension; Atenolol - pharmacology; Atenolol - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Blood Glucose - metabolism; Blood Pressure - drug effects; Blood Pressure - physiology; Captopril - analogs & derivatives; Captopril - pharmacology; Captopril - therapeutic use; Cardiology. Vascular system; Cardiovascular system; Cell Adhesion Molecules - blood; Cell Adhesion Molecules - drug effects; Cholesterol, HDL - blood; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Endothelial dysfunction; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Female; Heart Rate - drug effects; Heart Rate - physiology; Humans; hypertension; Hypertension - drug therapy; Hypertension - physiopathology; Male; Medical sciences; Middle Aged; oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pharmacology. Drug treatments; Ramipril - pharmacology; Ramipril - therapeutic use; Sulfhydryl Compounds - pharmacology; Sulfhydryl Compounds - therapeutic use; sulfhydryl group; Triglycerides - blood; Vasodilation - drug effects; Endothelial dysfunction; sulfhydryl group; adhesion molecules; hypertension; oxidative stress; ACE inhibitor; Human; Hypertension; Oxidative stress; Cardiovascular disease
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/j.amjhyper.2006.09.020

Oxidative inactivation of nitric oxide (NO) is regarded as an important cause of reduced endothelium-dependent vasodilation in essential hypertension. Because zofenopril, an angiotensin-converting enzyme (ACE) inhibitor with a sulfhydryl (SH) group, has demonstrated antioxidant properties and to reduce adhesion molecule expression in vitro, in this study we evaluated the effect of this drug in comparison with the carboxylic ACE inhibitor ramipril and the β-adrenoreceptor blocker atenolol on (1) circulating adhesion molecules and some oxidative stress parameters and (2) endothelium-dependent vasodilation in essential mildly hypertensive patients.
A total of 45 healthy subjects and 45 matched hypertensive patients participated in the study. Hypertensive patients were randomly treated with zofenopril (15 to 30 mg/d), ramipril (2.5 to 5 mg/d), and atenolol (50 to 100 mg/d). At baseline and after an 8-week therapy we evaluated blood pressure (BP) values, plasma and LDL hydroperoxides, plasma 8-isoprostanes, circulating levels of oxidized-(ox)LDL and of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1], and E-selectin). Furthermore, all patients underwent ultrasound detection of brachial artery reactivity and endothelium-dependent dilation (flow-mediated dilation, FMD) was evaluated.
All the treatments determined similar significant (
P < .001) reduction of both systolic and diastolic BP values. Plasma (
P < .01) and LDL hydroperoxides (
P < .01), plasma 8-isoprostanes (
P < .05), circulating oxLDL (
P < .05), and adhesion molecules (
P < .05) were significantly reduced only in patients receiving zofenopril. Similarly FMD was significantly increased (
P < .001) in the zofenopril-treated group.
Our results suggest that in mildly hypertensive patients without organ damage zofenopril, beyond its BP-lowering effects and through its sustained antioxidant activity, offers important advantages in reducing endothelial activation.