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

Hypertension. 2001 Feb;37(2 Pt 2):781-6. doi: 10.1161/01.hyp.37.2.781.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Aorta / drug effects
  • Blood Pressure / drug effects
  • Cyclic N-Oxides / pharmacology*
  • Desoxycorticosterone
  • Hypertension / chemically induced
  • Hypertension / prevention & control*
  • Male
  • Mineralocorticoids
  • NF-kappa B / metabolism
  • Nephritis / chemically induced
  • Nephritis / prevention & control*
  • Proline / analogs & derivatives*
  • Proline / pharmacology*
  • Protein Binding / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Spin Labels
  • Superoxides / metabolism
  • Thiocarbamates / pharmacology*
  • Time Factors

Substances

  • Antioxidants
  • Cyclic N-Oxides
  • Mineralocorticoids
  • NF-kappa B
  • Spin Labels
  • Thiocarbamates
  • Superoxides
  • prolinedithiocarbamate
  • Desoxycorticosterone
  • Proline
  • tempol