Rugale Caroline, Cordaillat Magali, Mimran Albert, Jover Bernard
Groupe Rein et Hypertension, Université Montpellier I, Montpellier, France.
J Renin Angiotensin Aldosterone Syst. 2005 Dec;6(3):154-60. doi: 10.3317/jraas.2005.023.
Angiotensin-converting enzyme inhibitors (ACE-Is) prevent target organ damage in several models of hypertension. The aim of this study was to assess the influence of the ACE-I enalapril (10 mg/kg(-1) per day, gavage) on the cardiovascular alterations and production of free radicals induced by chronic infusion of angiotensin II (Ang II, 200 ng/kg(-1) per minute, s.c.) in Sprague-Dawley rats. Enalapril was given concomitantly for the 10 days of Ang II infusion (prevention) or from day 10 to 17 of Ang II infusion (intervention). The influence of the NADPH oxidase inhibitor apocynin (600 mg/L(-1) in drinking water) was evaluated. Enalapril and apocynin had no effect on hypertension in the prevention and intervention studies. Enalapril prevented the increase in heart weight index (HWI), carotid cross-sectional area (CSA) and albuminuria induced by Ang II. Enalapril reduced HWI and albuminuria whereas CSA was not affected in the intervention study. Apocynin had effects comparable to enalapril. Both enalapril and apocynin reduced the overproduction of superoxide anion by the left ventricle and rise in advanced oxidation protein products induced by Ang II. Therefore, the antioxidant but not the antihypertensive effect of enalapril may participate in the prevention and treatment of the Ang II-induced cardiovascular and renal alterations.
血管紧张素转换酶抑制剂（ACE-Is）可在多种高血压模型中预防靶器官损伤。本研究旨在评估ACE-I依那普利（每天10 mg/kg-1，灌胃）对慢性输注血管紧张素II（Ang II，每分钟200 ng/kg-1，皮下注射）诱导的Sprague-Dawley大鼠心血管改变和自由基产生的影响。依那普利在Ang II输注的10天内同时给予（预防），或在Ang II输注的第10天至第17天给予（干预）。评估了NADPH氧化酶抑制剂阿朴吗啡（饮用水中600 mg/L-1）的影响。在预防和干预研究中，依那普利和阿朴吗啡对高血压均无影响。依那普利可预防Ang II诱导的心脏重量指数（HWI）增加、颈动脉横截面积（CSA）增加和蛋白尿。在干预研究中，依那普利降低了HWI和蛋白尿，但CSA未受影响。阿朴吗啡的作用与依那普利相当。依那普利和阿朴吗啡均可减少左心室超氧阴离子的过度产生以及Ang II诱导的晚期氧化蛋白产物的增加。因此，依那普利的抗氧化而非降压作用可能参与了Ang II诱导的心血管和肾脏改变的预防和治疗。
