Department of Surgery, Indiana University School of Medicine, 1001 W. 10th St., WD OPW 425F, Indianapolis, IN 46202-2879, USA.
Am J Physiol Heart Circ Physiol. 2009 Dec;297(6):H2227-33. doi: 10.1152/ajpheart.00325.2009. Epub 2009 Sep 25.
Previous work in our laboratory showed increased basal periarterial nitric oxide (NO) and H2O2 concentrations in the spontaneously hypertensive rat, characterized by oxidant stress, as well as impaired flow-mediated NO production that was corrected by a reduction of periarterial H2O2. Aging is also associated with an increase in vascular reactive oxygen species and results in abnormal vascular function. The current study was designed to assess the role of H2O2 in regulating NO production during vascular aging. In vivo, real-time NO and H2O2 concentrations were measured by microelectrodes in mesenteric arteries of retired breeder (aged; 8-12 mo) and young (2 to 3 mo) Wistar-Kyoto rats under conditions of altered flow. The results in aged rats revealed elevated basal NO (1,611+/-286 vs. 793+/-112 nM, P<0.05) and H2O2 concentrations (16+/-2 vs. 9+/-1 microM, P<0.05) and a flow-mediated increase in H2O2 but not NO production. Pretreatment of aged rats with the antioxidant apocynin lowered both basal H2O2 (8+/-1 microM) and NO (760+/-102 nM) to young levels and restored flow-mediated NO production. Similar results were obtained with the NAD(P)H oxidase inhibitor gp91ds-tat. In addition, acute incubation with topical polyethylene-glycolated catalase lowered the baseline NO concentration and restored flow-mediated NO production. Taken together, the data indicate that elevated baseline and suppressed flow-mediated NO production in aged Wistar-Kyoto rats are mediated by NAD(P)H oxidase-derived H2O2.
先前我们实验室的工作表明，氧化应激会导致自发性高血压大鼠的动脉周围基础型一氧化氮（NO）和 H2O2 浓度增加，同时还会损害血流介导的 NO 生成，而这种损害可以通过减少动脉周围的 H2O2 得到纠正。衰老也与血管活性氧的增加有关，并导致血管功能异常。本研究旨在评估 H2O2 在调节血管老化过程中 NO 生成中的作用。在体内，通过微电极实时测量 retired breeder（老龄；8-12 个月）和 young（2-3 个月）Wistar-Kyoto 大鼠肠系膜动脉中 NO 和 H2O2 的浓度，在改变血流的情况下进行研究。结果显示，老龄大鼠的基础型 NO（1,611+/-286 比 793+/-112 nM，P<0.05）和 H2O2 浓度（16+/-2 比 9+/-1 microM，P<0.05）升高，且 H2O2 产生的血流介导性增加，但 NO 生成没有增加。用抗氧化剂 apocynin 预处理老龄大鼠，可将基础型 H2O2（8+/-1 microM）和 NO（760+/-102 nM）降低到年轻水平，并恢复血流介导的 NO 生成。用 NAD(P)H 氧化酶抑制剂 gp91ds-tat 也得到了相似的结果。此外，急性用聚乙二醇化 catalase 处理可降低基线 NO 浓度并恢复血流介导的 NO 生成。综上所述，这些数据表明，老龄 Wistar-Kyoto 大鼠中升高的基础型和抑制的血流介导型 NO 生成是由 NAD(P)H 氧化酶衍生的 H2O2 介导的。
