NADPH oxidase inhibition attenuates oxidative stress but not hypertension produced by chronic ET-1
NADPH oxidase inhibition attenuates oxidative stress but not hypertension produced by chronic ET-1
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DOI：
10.1161/01.hyp.0000153051.56460.6a
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发表时间：
2005-02-01
期刊：
影响因子：
8.3
通讯作者：
Pollock, DM
中科院分区：
文献类型：
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作者：
Elmarakby, AA;Loomis, ED;Pollock, DM
进行实验以检验由慢性ET-1输注产生的高血压由NADPH氧化酶依赖性超氧化物产生介导的假设。通过遥测技术连续监测雄性Sprague道利大鼠的平均动脉压（MAP）。在基线测量后，将大鼠置于高盐饮食（8%NaCl）上，并植入渗透微型泵以输注ET-1（每分钟静脉内5 pmol/kg）12天。对照组大鼠仅维持高盐饮食。另一组大鼠在饮用水中注入ET-1并给予超氧化物歧化酶模拟物tempol（1 mmol/L）或NADPH氧化酶抑制剂apocynin（1.5 mmol/L）。与基线值相比，输注ET-1显著增加MAP（132 +/-3 vs 114 +/-2 mmHg，P < 0.05）。与基线值相比，tempol或夹竹桃麻素治疗对ET-1产生的MAP增加没有任何影响（分别为127 +/- 5 vs 113 +/- 2和130 +/- 3 vs 115 +/- 2 mmHg）。血浆8-异前列腺素，氧化应激的指标，在ET-1输注大鼠与大鼠相比，单独高盐饮食显着增加（128 +/- 33对51 +/- 5 pg/mL; P < 0.05）。tempol和夹竹桃麻素处理均显著减弱了ET-1诱导的血浆8-异前列烷的增加（分别为72 +/-10和61 +/-6 pg/mL）。同样，ET-1输注也显着增加主动脉超氧化物的产生（化学发光和二氢乙锭染色技术），这是防止tempol和夹竹桃素。这些数据提供的证据表明，慢性ET-1输注增加血管NADPH氧化酶依赖性超氧化物的生产，但不占慢性ET-1诱导的高血压。
Experiments were conducted to test the hypothesis that hypertension produced by chronic ET-1 infusion is mediated by NADPH oxidase-dependent superoxide production. Mean arterial pressure ( MAP) was continuously monitored in male Sprague Dawley rats by telemetry. After baseline measurements, rats were placed on a high-salt diet (8% NaCl) and osmotic minipumps were implanted to infuse ET-1 ( 5 pmol/kg per minute intravenous) for 12 days. Control rats were maintained on the high-salt diet only. Separate groups of rats were also infused with ET-1 and given the superoxide dismutase mimetic, tempol ( 1 mmol/L), or the NADPH oxidase inhibitor, apocynin (1.5 mmol/L), in the drinking water. Infusion of ET-1 significantly increased MAP when compared with baseline values ( 132 +/- 3 versus 114 +/- 2 mm Hg, P < 0.05). Neither tempol nor apocynin treatment had any effect on the increase in MAP produced by ET-1 when compared with baseline values ( 127 +/- 5 versus 113 +/- 2 and 130 +/- 3 versus 115 +/- 2 mm Hg, respectively). Plasma 8-isoprostane, an indicator of oxidative stress, was significantly increased in ET-1-infused rats compared with rats on a high-salt diet alone ( 128 +/- 33 versus 51 +/- 5 pg/mL; P < 0.05). Both tempol and apocynin treatment significantly attenuated the ET-1-induced increase in plasma 8-isoprostane ( 72 +/- 10 and 61 +/- 6 pg/mL, respectively). Similarly, ET-1 infusion also significantly increased aortic superoxide production ( chemiluminescence and dihydroethidium staining techniques), which was prevented by both tempol and apocynin. These data provide evidence that chronic ET-1 infusion increases vascular NADPH oxidase-dependent superoxide production but does not account for chronic ET-1-induced hypertension.