Long-term treatment with sulfhydryl angiotensin-converting enzyme inhibition reduces carotid intima-media thickening and improves the nitric oxide/oxidative stress pathways in newly diagnosed patients with mild to moderate primary hypertension.
BACKGROUND
Sulfhydryl angiotensin-converting enzyme (ACE) inhibitors exert antiatherosclerotic effects in preclinical models and antioxidant effects in patients. However, whether ACE inhibitors have any clinically significant antiatherogenic effects remains still debated.


OBJECTIVE
In mildly hypertensive patients, we evaluated the effect of the sulfhydryl ACE inhibitor zofenopril in comparison with the carboxylic ACE inhibitor enalapril on carotid atherosclerosis (intima-media thickness [IMT] and vascular lumen diameter) and systemic oxidative stress (nitrite/nitrate, asymmetrical dimethyl-l-arginine, and isoprostanes).


METHODS
In 2001, we started a small prospective randomized clinical trial on 48 newly diagnosed mildly hypertensive patients with no additional risk factors for atherosclerosis (eg, hyperlipidemia, smoke habit, familiar history of atherosclerosis-related diseases or diabetes). Patients were randomly assigned either to the enalapril (20 mg/d, n = 24) or the zofenopril group (30 mg/d, n = 24); the planned duration of the trial was 5 years. Carotid IMT and vascular lumen diameter were determined by ultrasonography for all patients at baseline and at 1, 3, and 5 years. Furthermore, nitrite/nitrate, asymmetrical dimethyl-l-arginine, and isoprostane levels were measured.


RESULTS
In our conditions, IMT of the right and left common carotid arteries was similar at baseline in both groups (P = NS). Intima-media thickness measurements until 5 years revealed a significant reduction in the zofenopril group but not in the enalapril group (P < .05 vs enalapril-treated group). This effect was coupled with a favorable nitric oxide/oxidative stress profile in the zofenopril group.


CONCLUSIONS
Long-term treatment with the sulfhydryl ACE inhibitor zofenopril besides its blood pressure-lowering effects may slow the progression of IMT of the carotid artery in newly diagnosed mildly hypertensive patients.
Napoli
Claudio
C
Department of General Pathology and Excellence Research Center on Cardiovascular Diseases, and Microbiology Section, 1st School of Medicine, II University of Naples, Naples, Italy. claudio.napoli@unina2.it
Bruzzese
Giuseppe
G
Ignarro
Louis J
LJ
Crimi
Ettore
E
de Nigris
Filomena
F
Williams-Ignarro
Sharon
S
Libardi
Sabina
S
Sommese
Linda
L
Fiorito
Carmela
C
Mancini
Francesco P
FP
Cacciatore
Francesco
F
Liguori
Antonio
A
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002216:Captopril / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002339:Carotid Arteries / Q000187:drug effects; D016893:Carotid Stenosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004656:Enalapril / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000187:drug effects*; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000187:drug effects*; D014463:Ultrasonography
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; C075750:8-epi-prostaglandin F2alpha; C044958:zofenopril; D009569:Nitric Oxide; D004656:Enalapril; D002216:Captopril; D015237:Dinoprost