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) 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-kappaB 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-kappaB-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-kappaB-binding activity compared with sham. These results suggest that antioxidants attenuate systolic blood pressure, suppress renal NF-kappaB-binding activity, and partly alleviate renal monocyte/macrophage infiltration in DOCA-salt hypertension.
Department of Physiology, the Vascular Biology Center, Medical College of Georgia, Augusta, GA, USA. rbeswick@umich.edu
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Beswick
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Zhang
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Marable
J D
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Catravas
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Hill
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Webb
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008901:Mineralocorticoids; D016328:NF-kappa B / Q000378:metabolism; D009393:Nephritis / Q000139:chemically induced / Q000517:prevention & control*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology*; D013997:Time Factors
D000975:Antioxidants; D003497:Cyclic N-Oxides; D008901:Mineralocorticoids; D016328:NF-kappa B; D013113:Spin Labels; D013859:Thiocarbamates; D013481:Superoxides; C066229:prolinedithiocarbamate; D003900:Desoxycorticosterone; D011392:Proline; C001803:tempol