Napoli Claudio, Bruzzese Giuseppe, Ignarro Louis J, Crimi Ettore, de Nigris Filomena, Williams-Ignarro Sharon, Libardi Sabina, Sommese Linda, Fiorito Carmela, Mancini Francesco P, Cacciatore Francesco, Liguori Antonio
Department of General Pathology and Excellence Research Center on Cardiovascular Diseases, and Microbiology Section, 1st School of Medicine, II University of Naples, Naples, Italy.
Am Heart J. 2008 Dec;156(6):1154.e1-8. doi: 10.1016/j.ahj.2008.09.006.
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.
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).
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.
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.
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.
巯基血管紧张素转换酶（ACE）抑制剂在临床前模型中具有抗动脉粥样硬化作用，在患者中具有抗氧化作用。然而，ACE抑制剂是否具有任何临床上显著的抗动脉粥样硬化作用仍存在争议。
在轻度高血压患者中，我们评估了巯基ACE抑制剂佐芬普利与羧基ACE抑制剂依那普利相比，对颈动脉粥样硬化（内膜中层厚度[IMT]和血管腔直径）和全身氧化应激（亚硝酸盐/硝酸盐、不对称二甲基-L-精氨酸和异前列腺素）的影响。
2001年，我们对48例新诊断的轻度高血压患者开展了一项小型前瞻性随机临床试验，这些患者没有动脉粥样硬化的其他危险因素（如高脂血症、吸烟习惯、动脉粥样硬化相关疾病家族史或糖尿病）。患者被随机分为依那普利组（20mg/d，n = 24）或佐芬普利组（30mg/d，n = 24）；试验计划持续时间为5年。在基线以及1年、3年和5年时，通过超声检查测定所有患者的颈动脉IMT和血管腔直径。此外，还测量了亚硝酸盐/硝酸盐、不对称二甲基-L-精氨酸和异前列腺素水平。
在我们的研究条件下，两组患者基线时左右颈总动脉的IMT相似（P = 无显著性差异）。直到5年的内膜中层厚度测量显示，佐芬普利组有显著降低，而依那普利组没有（与依那普利治疗组相比，P < 0.05）。这种作用与佐芬普利组中有利的一氧化氮/氧化应激情况相关。
巯基ACE抑制剂佐芬普利的长期治疗除了其降压作用外，可能会减缓新诊断的轻度高血压患者颈动脉IMT的进展。
