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.