Effect of sulfhydryl and non-sulfhydryl angiotensin-converting enzyme inhibitors on endothelial function in essential hypertensive patients.
BACKGROUND
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 beta-adrenoreceptor blocker atenolol on (1) circulating adhesion molecules and some oxidative stress parameters and (2) endothelium-dependent vasodilation in essential mildly hypertensive patients.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Pasini
Anna Fratta
AF
Department of Biomedical and Surgical Sciences (Medicina D), University of Verona, Verona, Italy.
Garbin
Ulisse
U
Nava
Maria Cristina
MC
Stranieri
Chiara
C
Pellegrini
Michele
M
Boccioletti
Veronica
V
Luchetta
Maria Laura
ML
Fabrizzi
Paolo
P
Lo Cascio
Vincenzo
V
Cominacini
Luciano
L
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000097:blood / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017257:Ramipril / Q000494:pharmacology / Q000627:therapeutic use*; D013438:Sulfhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D015815:Cell Adhesion Molecules; D008076:Cholesterol, HDL; D013438:Sulfhydryl Compounds; D014280:Triglycerides; C044958:zofenopril; D001262:Atenolol; D002216:Captopril; D017257:Ramipril