Superoxide excess in hypertension and aging - A common cause of endothelial dysfunction
Superoxide excess in hypertension and aging - A common cause of endothelial dysfunction
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DOI：
10.1161/01.hyp.37.2.529
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发表时间：
2001-02-01
期刊：
影响因子：
8.3
通讯作者：
Dominiczak, AF
中科院分区：
文献类型：
--
作者：
Hamilton, CA;Brosnan, MJ;Dominiczak, AF
有证据表明，人类的高血压和衰老同样会损害内皮功能，尽管机制尚不清楚。超氧阴离子(O-2(-))是一氧化氮(NO)生物利用度和内皮功能的主要决定因素。我们试图确定血压正常的Wistar-京都(WKY)和易卒中的自发性高血压大鼠(SHRSP)的内皮功能、O-2(-)和年龄之间的关系。雌性WKY和SHRSP分别在3~4个月(青年)和9~12个月(大)时摘除主动脉环。用免疫组织化学方法检测去内皮前后及与N-G-硝基-L-精氨酸甲酯、二苯基二碘甲烷或apocynin孵育前后主动脉环产生O-2(-)的情况，并以此作为NAD(P)H氧化酶表达的标志。老年WKY的NO生物利用度显著低于年轻WKY(P=0.0009)，老年SHRSP的NO生物利用度显著低于年轻SHRSP(P=0.005)。老年WKY的O-2(-)世代显著多于青年WKY(P=0.0001)。去内皮和N-G-硝基-L-精氨酸甲酯处理使陈旧性自发性高血压大鼠的O2(-)生成显著减少(P分别为0.009和0.001)。二苯碘显著减少12个月龄WKY(P=0.008)和12个月龄SHRSP(P=0.009)的O-2(-)生成。Apoynin抑制老年WKY(P=0.038)和SHRSP(P=0.028)产生的O-2(-)，与年轻动物相比，老年动物p22Phox增加。我们得出结论，在女性WKY和SHRSP中，没有生物利用度随着年龄的增加而降低。WKY的O-2(-)生成量随年龄增长而增加，SHRSP的O-2(-)生成量较高，可能通过清除NO来减少NO的生成。NAD(P)H氧化酶可能参与了O-2(-)的增龄增加。
There is evidence in humans that hypertension and aging similarly impair endothelial function, although the mechanism remains unclear. Superoxide anion (O-2(-)) is a major determinant of nitric oxide (NO) bioavailability and thus endothelial function. We sought to determine the relationship between endothelial function, O-2(-), and age in normotensive Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Aortic rings were removed from female WKY and SHRSP at 3 to 4 months (young) and 9 to 12 months (old). O-2(-) generation by aortic rings was measured before and after removal of the endothelium or incubation with N-G nitro-l-arginine methyl ester, diphenyleneiodonium, or apocynin, Levels of p22phox were studied with immunohistochemistry and used as a marker of NAD(P)H oxidase expression. NO bioavailability was significantly lower in old WKY compared with young WKY (P = 0.0009) and in old SHRSP compared with young SHRSP (P = 0.005). O-2(-) generation was significantly greater in old WKY compared with young WKY (P = 0.0001). Removal of the endothelium and N-G nitro-L-arginine methyl ester treatment resulted in a significant reduction in O-2(-) generation in old SHRSP (P = 0.009 and 0.001, respectively). Diphenyleneiodonium significantly reduced O-2(-) generation in 12-month WKY (P = 0.008) and 12-month SHRSP (P = 0.009). Apocynin attenuated O-2(-) generation by older WKY (P = 0.038) and SHRSP (P = 0.028), p22phox was increased in older animals compared with young. We conclude that NO bioavailability decreases with age in female WKY and SHRSP. O-2(-) generation increases with age in WKY and is higher in SHRSP and may contribute to the reduced NO by scavenging. NAD(P)H oxidase may contribute to the age-related increase in O-2(-).