Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation - Contribution to alterations of vasomotor tone
Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation - Contribution to alterations of vasomotor tone
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DOI：
10.1172/jci118623
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发表时间：
1996-04-15
影响因子：
15.9
通讯作者：
Harrison, DG
中科院分区：
文献类型：
--
作者：
Rajagopalan, S;Kurz, S;Harrison, DG
我们检验了血管紧张素II诱导的高血压与血管超氧阴离子（O₂⁻）产生增加相关这一假说，并对该过程中涉及的氧化酶进行了表征。血管紧张素II（0.7毫克/千克/天）输注使收缩压升高，血管超氧阴离子产生增加一倍（通过光泽精化学发光法评估），且主要来自血管中膜。去甲肾上腺素（NE，2.75毫克/千克/天）输注产生相似程度的高血压，但未增加血管超氧阴离子产生。使用各种酶抑制剂和血管匀浆的研究表明，血管紧张素II输注激活的超氧阴离子的主要来源是一种依赖NADH/NADPH的膜结合氧化酶。血管紧张素II诱导的高血压（而非去甲肾上腺素诱导的高血压）与乙酰胆碱、钙离子载体A23187和硝酸甘油诱导的舒张功能受损有关。通过用脂质体包裹的超氧化物歧化酶处理血管，这些舒张功能得到了不同程度的纠正。当氯沙坦与血管紧张素II同时给药时，血管超氧阴离子产生和舒张功能恢复正常，这表明血管紧张素1型受体在这些过程中起作用。我们得出结论，与血管紧张素II循环水平升高相关的高血压类型可能具有其他高血压类型所没有的独特血管效应，因为它们通过NADH/NADPH氧化酶激活增加了血管平滑肌超氧阴离子的产生。
We tested the hypothesis that angiotensin II-induced hypertension is associated with an increase in vascular . O-2(-) production, and characterized the oxidase involved in this process, Infusion of angiotensin II (0.7 mg/kg per d) increased systolic blood pressure and doubled vascular . O-2(-) production (assessed by lucigenin chemiluminescence), predominantly from the vascular media, NE infusion (2.75 mg/kg per d) produced a similar degree of hypertension, but did not increase vascular . O-2(-) production, Studies using various enzyme inhibitors and vascular homogenates suggested that the predominant source of . O-2(-) activated by angiotensin II infusion is an NADH/NADPH-dependent, membrane-bound oxidase, Angiotensin II-, but not NE-, induced hypertension was associated with impaired relaxations to acetylcholine, the calcium ionophore A23187, and nitroglycerin. These relaxations were variably corrected by treatment of vessels with liposome-encapsulated superoxide dismutase, When Losartan was administered concomitantly with angiotensin II, vascular . O-2(-) production and relaxations were normalized, demonstrating a role for the angiotensin type-1 receptor in these processes, We conclude that forms of hypertension associated with elevated circulating levels of angiotensin II may have unique vascular effects not shared by other forms of hypertension because they increase vascular smooth muscle . O-2(-) production via NADH/NADPH oxidase activation.