Department of Nephrology and Hypertension, Eliachar Research Laboratory, Western Galilee Hospital, Naharyia, Israel.
Hypertension. 2010 Feb;55(2):353-62. doi: 10.1161/HYPERTENSIONAHA.109.144154. Epub 2010 Jan 11.
In the Sabra rat, oxidative stress (OS) and inflammation precede the development of hypertension. Inhibition of the phagocytic NADPH oxidase attenuates the rise in blood pressure. The present study was set to identify possible priming agents for this enzyme and to test the hypothesis that the phagocytic NADPH oxidase contributes to OS and inflammation. Sabra salt-sensitive and Sabra salt-resistant rats were salt loaded or provided regular chow for 60 days with or without apocynin to inhibit NADPH oxidase. Levels of interleukin 6, tumor necrosis factor-alpha, and interferon-gamma served as indices of inflammation. Extracellular and intracellular levels of the polymorphonuclear leukocyte tumor necrosis factor-alpha receptors (p55 and p75) were assessed by flow cytometry in young and adult rats. NADPH oxidase activity and expression of p47phox were measured in polymorphonuclear leukocytes and aortic rings. Malondialdehyde and carbonylated fibrinogen served as indices of OS. Inflammatory and OS indices excluding interferon-gamma were higher in the hypertensive state and reduced by apocynin. Levels of malondialdehyde and tumor necrosis factor-alpha were elevated already in the prehypertensive state. No differences were found in the levels of p75. The extracellular expression of p55 was higher in adult Sabra salt-resistant compared with Sabra salt-sensitive rats (7.46+/-2.2% versus 2.1+/-0.5%; P<0.05), whereas levels of the intracellular p55 were higher in adult Sabra salt-sensitive rats (3.2+/-2% versus 1.1+/-0.5%; P<0.05). In young normotensive rats, the extracellular levels of p55 were higher in Sabra salt-sensitive compared with Sabra salt-resistant rats (10.6+/-5.2% versus 2.9+/-1.5%; P<0.01). Tumor necrosis factor-alpha plays a role in activation of the polymorphonuclear leukocyte NADPH oxidase, thereby contributing to systemic OS, inflammation, and the development of hypertension in this model.
在沙巴大鼠中，氧化应激（OS）和炎症先于高血压的发展。吞噬型 NADPH 氧化酶的抑制可减轻血压升高。本研究旨在确定该酶的可能引发剂，并检验吞噬型 NADPH 氧化酶有助于 OS 和炎症的假设。沙巴盐敏感型和沙巴盐抵抗型大鼠进行盐负荷或给予常规饮食 60 天，同时给予或不给予 apocynin 以抑制 NADPH 氧化酶。白细胞介素 6、肿瘤坏死因子-α和干扰素-γ水平作为炎症指标。通过流式细胞术评估年轻和成年大鼠中性粒细胞肿瘤坏死因子-α受体（p55 和 p75）的细胞外和细胞内水平。在中性粒细胞和主动脉环中测量 NADPH 氧化酶活性和 p47phox 的表达。丙二醛和羰基化纤维蛋白原作为 OS 的指标。在高血压状态下，除干扰素-γ外，炎症和 OS 指标升高，并被 apocynin 降低。在高血压前期，丙二醛和肿瘤坏死因子-α水平升高。p75 水平无差异。与沙巴盐敏感型大鼠相比，成年沙巴盐抵抗型大鼠中性粒细胞表面 p55 的细胞外表达更高（7.46+/-2.2%比 2.1+/-0.5%；P<0.05），而成年沙巴盐敏感型大鼠中性粒细胞内 p55 的水平更高（3.2+/-2%比 1.1+/-0.5%；P<0.05）。在年轻的正常血压大鼠中，沙巴盐敏感型大鼠中性粒细胞表面 p55 的细胞外水平高于沙巴盐抵抗型大鼠（10.6+/-5.2%比 2.9+/-1.5%；P<0.01）。肿瘤坏死因子-α在中性粒细胞 NADPH 氧化酶的激活中起作用，从而导致该模型中的全身性 OS、炎症和高血压的发展。
