We previously reported increased monocyte/macrophage infiltration, reactive
oxygen species accumulation, and nuclear factor-kappaB (NF-kappaB) activat
ion in mineralocorticoid (deoxycorticosterone acetate [DOCA]) hypertensive
rats. We tested the hypothesis that prolonged antioxidant administration in
hibits superoxide accumulation, lowers blood pressure, and reduces NF-kappa
B activation in DOCA-salt hypertensive rats. DOCA rats exhibited a signific
ant increase in systolic blood pressure compared with sham rats, Aortic rin
gs from DOCA rats exhibited increased superoxide (O-2(-)) production compar
ed with sham rats. In addition, the treatment of DOCA rats with pyrrolidine
dithiocarbamate (PDTC) or 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (Temp
ol) caused a significant decrease in systolic blood pressure and aortic sup
eroxide accumulation. Monocyte/macrophage infiltration was also significant
ly decreased in DOCA rats treated with PDTC or Tempol compared with untreat
ed DOCA rats. NF-kappaB-binding activity was significantly greater in untre
ated DOCA rats than in either sham rats or PDTC- or Tempol-treated DOCA rat
s. Also, DOCA rats treated with Tempol exhibited no significant difference
in NF-kappaB-binding activity compared with sham. These results suggest tha
t antioxidants attenuate systolic blood pressure, suppress renal NF-kappaB-
binding activity, and partly alleviate renal monocyte/macrophage infiltrati
on in DOCA-salt hypertension.