NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat
NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat
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DOI：
10.1161/hy1101.093423
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发表时间：
2001-11-01
期刊：
影响因子：
8.3
通讯作者：
Webb, RC
中科院分区：
文献类型：
--
作者：
Beswick, RA;Dorrance, AM;Webb, RC
我们之前报道了矿化皮质激素（醋酸脱氧皮质酮[DOCA]盐）高血压大鼠主动脉活性氧（ROS）的产生增加。在本研究中，我们验证了NADH/NADPH氧化酶负责增加doca盐大鼠主动脉中ROS生成的假设，即超氧化物（O-2(-)）。一氧化氮合酶抑制剂n -硝基- l -精氨酸和黄嘌呤氧化酶抑制剂别嘌呤醇对doca盐大鼠主动脉环的处理没有显著改变O-2（-）的产生。此外，与假手术大鼠相比，doca盐大鼠主动脉去内皮化不影响O-2（-）的产生。因此，黄嘌呤氧化酶和解偶联内皮NO合酶与doca盐大鼠O-2（-）生成增加无关。相比之下，与假手术大鼠相比，NADPH氧化酶抑制剂罗布麻素显著降低了doca盐大鼠主动脉环中O-2（-）的产生。此外，长期给予doca盐大鼠（饮用水中，1.5 mmol/L， 28天）与单独给予doca盐处理的大鼠相比，收缩压明显降低。此外，与未处理的DOCA-salt大鼠相比，经夹竹桃素处理28天的DOCA-salt大鼠主动脉环中O-2（-）的产生减少。逆转录聚合酶链反应（RT-PCR）分析表明，与假手术大鼠相比，doca盐大鼠NADPH氧化酶亚基p22phox的mRNA水平显著升高。这些发现表明，NADPH氧化酶升高，导致O-2（-）产生增加，并可能导致doca盐高血压大鼠血压升高。
We previously reported increased aortic reactive oxygen species (ROS) production in mineralocorticoid (deoxycorticosterone acetate [DOCA]-salt) hypertensive rats. In the present study, we tested the hypothesis that NADH/NADPH oxidase is responsible for increased ROS production, namely superoxide (O-2(-)), in aorta from the DOCA-salt rat. Treatment of aortic rings from DOCA-salt rats with the NO synthase inhibitor N-nitro-L-arginine and the xanthine oxidase inhibitor allopurinol did not significantly change O-2(-) production. Furthermore, de-endothelialization of aorta from DOCA-salt rats did not affect O-2(-) production compared with that of sham-operated rats. Thus, xanthine oxidase and uncoupled endothelial NO synthase were not responsible for increased O-2(-) production in the DOCA-salt rats. In contrast, treatment with the NADPH oxidase inhibitor apocynin significantly decreased O-2(-) production in aortic rings from DOCA-salt rats compared with sham-operated rats. Moreover, long-term administration of apocynin (in drinking water, 1.5 mmol/L, 28 days) to DOCA-salt rats significantly decreased systolic blood pressure compared with that of rats treated with DOCA-salt alone. Furthermore, O-2(-) production in aortic rings from DOCA-salt rats treated with apocynin for 28 days was reduced compared with that of untreated DOCA-salt rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated that DOCA-salt rats have significantly greater mRNA levels of the NADPH oxidase subunit p22phox than do sham-operated rats. These findings suggest that NADPH oxidase is increased and is responsible for increased O-2(-) production and possibly contributes to increased blood pressure in the DOCA-salt hypertensive rat.