Diep Quy N, Amiri Farhad, Touyz Rhian M, Cohn Jeffrey S, Endemann Dierk, Neves Mario Fritsch, Schiffrin Ernesto L
CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.
Hypertension. 2002 Dec;40(6):866-71. doi: 10.1161/01.hyp.0000037969.41360.cc.
Docosahexaenoic acid (DHA), a peroxisome proliferator-activated receptor-alpha (PPARalpha) activator, reduces blood pressure (BP) in some hypertensive models by unclear mechanisms. We tested the hypothesis that DHA would prevent BP elevation and improve vascular dysfunction in angiotensin (Ang) II-infused rats by modulating of NADPH oxidase activity and inflammation in vascular wall. Sprague-Dawley rats received Ang II (120 ng/kg per minute SC) with or without DHA (2.5 mL of oil containing 40% DHA/d PO) for 7 days. Systolic BP (mm Hg), elevated in Ang II-infused rats (172+/-3) versus controls (108+/-2, P<0.01), was reduced by DHA (112+/-4). In mesenteric small arteries studied in a pressurized myograph, media/lumen ratio was increased (P<0.05) and acetylcholine-induced relaxation impaired in Ang II-infused rats (P<0.05); both were normalized by DHA. In blood vessels of Ang II-infused rats, NADPH oxidase activity measured by chemiluminescence and expression of adhesion molecules intercellular adhesion molecule and vascular cell adhesion molecule-1 were significantly increased. These changes were abrogated by DHA. PPARalpha activator DHA attenuated the development of hypertension, corrected structural abnormalities, and improved endothelial dysfunction induced by Ang II. These effects are associated with decreased oxidative stress and inflammation in the vascular wall.
二十二碳六烯酸（DHA）是一种过氧化物酶体增殖物激活受体α（PPARα）激活剂，在一些高血压模型中可降低血压（BP），但其机制尚不清楚。我们检验了这样一个假设，即DHA可通过调节血管壁中NADPH氧化酶活性和炎症反应，预防血管紧张素（Ang）II灌注大鼠的血压升高并改善血管功能障碍。将Sprague-Dawley大鼠分为两组，一组接受Ang II（120 ng/kg每分钟皮下注射），另一组在接受Ang II的同时给予DHA（每天口服含40%DHA的油2.5 mL），持续7天。与对照组（108±2，P<0.01）相比，接受Ang II灌注的大鼠收缩压（mmHg）升高（172±3），而DHA可使其降低（112±4）。在压力肌动描记器中研究的肠系膜小动脉中，接受Ang II灌注的大鼠中膜/管腔比值增加（P<0.05），乙酰胆碱诱导的舒张功能受损（P<0.05）；而DHA可使两者恢复正常。在接受Ang II灌注的大鼠血管中，通过化学发光法测定的NADPH氧化酶活性以及细胞间黏附分子和血管细胞黏附分子-1等黏附分子的表达均显著增加。这些变化被DHA消除。PPARα激活剂DHA减轻了高血压的发展，纠正了结构异常，并改善了由Ang II诱导的内皮功能障碍。这些作用与血管壁氧化应激和炎症反应的降低有关。
