特异性AT_1受体阻滞剂卢沙坦对清醒大鼠AⅡ和NE介导的高血压及脂质过氧化反应的作用

Effects of losartan on high blood pressure and lipid super-oxide induced by A II and norepinephrine in conscious rats

目的 探讨阻断AT_1受体对AⅡ和去甲肾上腺素(NE)介导的高血压及脂质过氧化反应的影响。方法 成年Wistar大鼠36只,麻醉,颈动脉、颈静脉分别插入抗凝管并固定,清醒活动后按实验设计随机分6组(n=6)给予相应处理,处理前后均测定颈动脉平均压及血浆MDA、AⅡ及SOD水平。结果 1组给药前后各测定指标无明显变化,2、3组给药30分钟后血压上升显著且稳定持续至给药完毕,给药后血浆MDA明显升高,SOD明显下降,4、5两组给药后动脉血压均明显低于2、3组。但4组的降低幅度大于5组,且该组给药前后MDA及SOD水平并无显著改变,而5组给药前后的MDA仍然较高,SOD下降亦较明显,其上升或下降幅度均不及2组。6组虽未介入卢沙坦,但其给药后血压上升的幅度却明显低于2、3组,而该组MDA含量并无明显改变。结论 特异性AT_1受体阻滞剂卢沙坦对AⅡ介导的高血压及脂质过氧化反应有明显对抗作用,而对NE介导的高血压虽有降低效应,但对其引发的脂质过氧化并无对抗作用,提示AⅡ介导的高血压可能有其它因素参与,大剂量SOD输注不仅消除了AⅡ介导的脂质过氧化反应,同时也明显减弱了其升压作用,提示AⅡ的升压作用可能与脂质过氧化反应有关。且可能由AT_1受体所介导。

Objective To explore the effects of losartan on exogenous A Ⅱ or NE-produced hype-tension and Lipid superoxide in conscious rats. Methods 36 rats were divided into six Groups. Hyper-stension and Lipid superoxide were Produced by 10 hours intravenous infusion of angiotension Ⅱ (A Ⅱ) or norepinephrine (NE). Rats were also treated with intravenous infusion of Losartan or exogenous superoxide dismutase (SOD). Mean arterial pressure (MAP) , Serum Malondialdehyde (MDA), A II and sod content were measured. Results A Ⅱ infusion not only significantly increased MAP and MDA, but also decreased SOD content to a similar extent as NE infusion. A Ⅱ + Losartan infusion significantly decreased MAP and MDA level, and increased SOD content compared with NW+Losar-tan infusion. SOD+ A Ⅱ infusion significanfy decreased MAP and MDA compared with A Ⅱ infusion or NE infusion alone. Conclusion A Ⅱ-produced Lipid superoxide plays an important role in A Ⅱ-in-duced hypertension, and it can be mediated by AT1 receiptor. SOD infusion can attenuated the rise of blood pressure produced by AIL.