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267 ENHANCED SUPEROXIDE ACTIVITY INDUCES SALT SENTSITIVITY IN ENDOGENOUS NITRIC OXIDE SYNTHASE KNOCKOUT MICE.
  1. A. Hess1,
  2. L. Kopkan1,
  3. A. Castillo1,
  4. D. S.A. Majid1
  1. 1Department of Physiology, Tulane University Health Sciences Center, Hypertension and Renal Center of Excellence, New Orleans, LA

Abstract

Nitric oxide (NO) synthase inhibition enhances superoxide (O2) activity. The present study was conducted to examine the hypothesis that salt sensitivity is induced by superoxide (O2) activity that is enhanced due to a deficiency in endogenous nitric oxide (NO) production. Male knockout (KO) mice lacking the gene for endothelial NO synthase and their genetic background wild-type C57BL6J mice (WT) were fed a diet containing either normal salt (NS, 0.4% NaCl) or high salt (HS, 4% NaCl) and treated with or without a O2 scavenger, tempol (400 mg/L), in drinking water for 2 weeks. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography and urine collection was performed in metabolic cages on every third day during the 2-week experimental period. Urinary 8-isoprostane concentration (a marker for oxidative stress) was measured by ELISA kit (Cayman). Baseline SBP values in KO groups were significantly higher compared with WT groups (138 ± 5 vs 116 ± 4 mm Hg). At the end of the 2-week period, there was no significant difference in SBP between the tempol-treated and untreated WT groups with NS intake. However, SBP was significantly lower in tempol-treated KO mice compared with untreated KO mice fed on NS diets (131 ± 2 vs 142 ± 3 mm Hg). HS intake had no effect on SBP in untreated and treated WT groups; however, SBP was significantly increased in KO with HS intake (154 ± 4 mm Hg) over the 2-week period. Tempol significantly attenuated the effect of HS on SBP in the KO group (139 ± 2 mm Hg). There were no differences in baseline urinary 8-isoprostane excretion (UISOV) between WT and KO mice. However, at the end of 2 weeks, compared with WT and KO with NS intake (2.2 ± 0.1 and 2.4 ± 0.3 ng/d, respectively), UISOV was increased in both WT and KO groups with HS intake (2.9 ± 0.3 and 3.6 ± 0.2 ng/d, respectively), the increase in UISOV being greater in KO compared with WT. Tempol attenuated UISOV in both WT and KO with HS intake (2.5 ± 0.1 and 2.9 ± 0.2 ng/d). These data suggest that, in the condition of eNOS enzyme deficiency, dietary high-salt intake induces enhanced O2 activity that contributes to the development of salt-sensitive hypertension.

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