Long-Term Antioxidant Administration Attenuates Mineralocorticoid Hypertension and Renal Inflammatory Response

Abstract

We previously reported increased monocyte/macrophage infiltration, reactive oxygen species accumulation, and nuclear factor-κB (NF-κB) activation in mineralocorticoid (deoxycorticosterone acetate [DOCA]) hypertensive rats. We tested the hypothesis that prolonged antioxidant administration inhibits superoxide accumulation, lowers blood pressure, and reduces NF-κB activation in DOCA-salt hypertensive rats. DOCA rats exhibited a significant increase in systolic blood pressure compared with sham rats. Aortic rings from DOCA rats exhibited increased superoxide (O 2 − ) production compared with sham rats. In addition, the treatment of DOCA rats with pyrrolidinedithiocarbamate (PDTC) or 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (Tempol) caused a significant decrease in systolic blood pressure and aortic superoxide accumulation. Monocyte/macrophage infiltration was also significantly decreased in DOCA rats treated with PDTC or Tempol compared with untreated DOCA rats. NF-κB–binding activity was significantly greater in untreated DOCA rats than in either sham rats or PDTC- or Tempol-treated DOCA rats. Also, DOCA rats treated with Tempol exhibited no significant difference in NF-κB–binding activity compared with sham. These results suggest that antioxidants attenuate systolic blood pressure, suppress renal NF-κB–binding activity, and partly alleviate renal monocyte/macrophage infiltration in DOCA-salt hypertension.