Role of superoxide in angiotensin II-induced but not catecholamine-induced hypertension
Role of superoxide in angiotensin II-induced but not catecholamine-induced hypertension
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DOI：
10.1161/01.cir.95.3.588
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发表时间：
1997-02-04
期刊：
影响因子：
37.8
通讯作者：
Harrison, DG
中科院分区：
文献类型：
--
作者：
Laursen, JB;Rajagopalan, S;Harrison, DG
背景超氧化物(.)的主要来源O-2(-))是一种依赖于NADH/NADPH的膜结合氧化酶。我们之前已经证明，这种氧化酶在血管紧张素II中被激活，但在去甲肾上腺素诱导的高血压中不被激活。我们假设与慢性血管紧张素Il升高相关的高血压可能部分由血管引起。方法和结果我们用血管紧张素II或去甲肾上腺素连续5天输注的方法造成大鼠高血压。同时给予脂质体包裹的超氧化物歧化酶(SOD)或空脂质体治疗。在基线条件下和注射乙酰胆碱或硝普钠期间，测量清醒大鼠的动脉压。血管方面的。用荧光素化学发光法检测O-2(-)的产生。体外血管松弛在器官室内进行检测。注射去甲肾上腺素使血压升高的程度与注射血管紧张素II相似(分别为179+/-5和189+/-4毫米汞柱)。相反，血管紧张素II诱导的高血压与血管增加有关。O-2(-)的产生，而去甲肾上腺素引起的高血压不产生。注射血管紧张素II的大鼠经脂质体包裹的超氧化物歧化酶可降低血压50毫米汞柱，而对对照组或去甲肾上腺素诱导的高血压大鼠的血压无影响。同样，脂质体包裹的SOD在体内增强了血管紧张素II治疗的大鼠对乙酰胆碱的降压反应，在体外增强了对内皮依赖性血管扩张剂的反应。结论慢性升高的血管紧张素II引起的高血压部分是由血管紧张素II引起的。O-2(-)，可能是通过降解内皮源性NO。血管增多。O-2(-)可能参与高肾素/血管紧张素II状态下的血管疾病。
Background The major source of superoxide (. O-2(-)) in vascular tissues is an NADH/NADPH-dependent, membrane-bound oxidase. We have previously shown that this oxidase is activated in angiotensin II- but not norepinephrine-induced hypertension. We hypothesized that hypertension associated with chronically elevated angiotensin Il might be caused in part by vascular . O-2(-) production.Methods and Results We produced hypertension in rats by a 5-day infusion of angiotensin II or norepinephrine. Rats were also treated with liposome-encapsulated superoxide dismutase (SOD) or empty liposomes. Arterial pressure was measured in conscious rats under baseline conditions and during bolus injections of either acetylcholine or nitroprusside. Vascular . O-2(-) production was assessed by lucigenin chemiluminescence. In vitro vascular relaxations were examined in organ chambers. Norepinephrine infusion increased blood pressure to a similar extent as angiotensin II infusion (179+/-5 and 189+/-4 mm Hg, respectively). In contrast, angiotensin II-induced hypertension was associated with increased vascular . O-2(-) production, whereas norepinephrine-induced hypertension was not. Treatment with liposome-encapsulated SOD reduced blood pressure by 50 mm Hg in angiotensin II-infused rats while having no effect on blood pressure in control rats or rats with norepinephrine-induced hypertension. Similarly, liposome-encapsulated SOD enhanced in vivo hypotensive responses to acetylcholine and in vitro responses to endothelium-dependent vasodilators in angiotensin II-treated rats.Conclusions Hypertension caused by chronically elevated angiotensin II is mediated in part by . O-2(-), likely via degradation of endothelium-derived NO .. Increased vascular . O-2(-) may contribute to vascular disease in high renin/angiotensin II states.