Tumor Necrosis Factor-α: A Possible Priming Agent for the Polymorphonuclear Leukocyte–Reduced Nicotinamide-Adenine Dinucleotide Phosphate Oxidase in Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2010-02, Vol.55 (2), p.353-362
• Main Authors: Mazor, Rafi, Itzhaki, Osnat, Sela, Shifra, Yagil, Yoram, Cohen-Mazor, Meital, Yagil, Chana, Kristal, Batya
• Format: Article
• Language: English
• Subjects: Acetophenones - pharmacology; Analysis of Variance; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure Determination; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Cytokines - blood; Cytokines - metabolism; Disease Models, Animal; Gene Expression Regulation; Hypertension - enzymology; Immunohistochemistry; Malondialdehyde - metabolism; Medical sciences; NADPH Oxidases - drug effects; NADPH Oxidases - metabolism; Neutrophils - enzymology; Neutrophils - physiology; Oxidative Stress - physiology; Probability; Random Allocation; Rats; Rats, Inbred SHR; Sodium Chloride, Dietary - pharmacology; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.109.144154

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-α, and interferon-γ served as indices of inflammation. Extracellular and intracellular levels of the polymorphonuclear leukocyte tumor necrosis factor-α 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-γ were higher in the hypertensive state and reduced by apocynin. Levels of malondialdehyde and tumor necrosis factor-α 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