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阿朴肉桂酸抑制 ADMA/NO 通路以外途径减轻年轻自发性高血压大鼠的氧化应激和高血压

Apocynin attenuates oxidative stress and hypertension in young spontaneously hypertensive rats independent of ADMA/NO pathway.

机构信息

Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.

出版信息

Free Radic Res. 2012 Jan;46(1):68-76. doi: 10.3109/10715762.2011.639069. Epub 2011 Nov 29.

DOI:10.3109/10715762.2011.639069
PMID:22070348
Abstract

Both NADPH oxidase-derived reactive oxygen species (ROS) and asymmetric dimethylarginine (ADMA) are increased in hypertension. Apocynin, an NADPH oxidase inhibitor, could inhibit ROS, thus we tested whether apocynin can block NADPH oxidase and prevent increases of ADMA and blood pressure (BP) in spontaneously hypertensive rats (SHRs). SHRs and Wistar Kyoto (WKY) rats, aged 4 weeks, were assigned to four groups: untreated SHRs and WKY rats, SHRs and WKY rats that received 2.5 mM apocynin for 8 weeks. BP was significantly higher in SHRs compared to WKY rats, which was attenuated by apocynin. Apocynin prevented p47phox translocation in SHR kidneys, but not the increase of superoxide and H(2)O(2). Additionally, apocynin did not protect SHRs against increased ADMA. Apocynin blocks NADPH oxidase to attenuate hypertension, but has little effect on the ADMA/nitric oxide (NO) pathway in young SHRs. The reduction of ROS and the preservation of NO simultaneously might be a better approach to restoring ROS-NO balance to prevent hypertension.

摘要

活性氧(ROS)和不对称二甲基精氨酸(ADMA)均在高血压中增加。烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶抑制剂可以抑制 ROS,因此我们检测了烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶抑制剂是否可以阻断 NADPH 氧化酶并预防自发性高血压大鼠(SHR)中 ADMA 和血压(BP)的升高。4 周龄的 SHR 和 Wistar Kyoto(WKY)大鼠被分为四组:未治疗的 SHR 和 WKY 大鼠,接受 2.5mM 烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶抑制剂治疗 8 周的 SHR 和 WKY 大鼠。与 WKY 大鼠相比,SHR 的 BP 明显升高,而烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶抑制剂则减轻了这一现象。烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶抑制剂可防止 SHR 肾脏中 p47phox 的易位,但不能防止超氧化物和 H(2)O(2)的增加。此外,烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶抑制剂不能防止 SHR 中 ADMA 的增加。烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶抑制剂可阻断 NADPH 氧化酶以减轻高血压,但对年轻 SHR 中的 ADMA/一氧化氮(NO)途径几乎没有影响。同时减少 ROS 和保存 NO 可能是恢复 ROS-NO 平衡以预防高血压的更好方法。

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