Long-term antioxidant administration attenuates mineralocorticoid hypertension and renal inflammatory response

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.