A high-salt diet further impairs age-associated declines in cognitive, behavioral, and cardiovascular functions in male Fischer brown Norway rats

J Nutr. 2013 Sep;143(9):1406-13. doi: 10.3945/jn.113.177980. Epub 2013 Jul 17.


Aging-associated declines in cognitive, emotional, and cardiovascular function are well known. Environmental stress triggers critical changes in the brain, further compromising cardiovascular and behavioral health during aging. Excessive dietary salt intake is one such stressor. Here, we tested the effect of high salt (HS) on anxiety, learning-memory function, and blood pressure (BP) in male Fischer brown Norway (FBN) rats. Adult (A; 2 mo) and old (O; 20 mo) male rats were fed normal-salt (NS; 0.4% NaCl) or HS (8% NaCl) diets for 4 wk after being implanted with telemeter probes for conscious BP measurement. Thereafter, tests to assess anxiety-like behavior and learning-memory were conducted. The rats were then killed, and samples of plasma, urine, and brain tissue were collected. We found that systolic BP was higher in O-NS (117 ± 1.2 mm Hg) than in A-NS (105 ± 0.8 mm Hg) rats (P < 0.05). Furthermore, BP was higher in O-HS (124 ± 1.4 mm Hg) than in O-NS (117 ± 1.2 mm Hg) rats (P < 0.05). Moreover, anxiety-like behavior (light-dark and open-field tests) was not different between A-NS and O-NS rats but was greater in O-HS rats than in A-NS, O-NS, or A-HS rats (P < 0.05). Short-term memory (radial arm water maze test) was similar in A-NS and O-NS rats but was significantly impaired in O-HS rats compared with A-NS, O-NS, or A-HS rats (P < 0.05). Furthermore, oxidative stress variables (in plasma, urine, and brain) as well as corticosterone (plasma) were greater in O-HS rats when compared with A-NS, O-NS, or A-HS rats (P < 0.05). The antioxidant enzyme glyoxalase-1 expression was selectively reduced in the hippocampus and amygdala of O-HS rats compared with A-NS, O-NS, or A-HS rats (P < 0.05), whereas other antioxidant enzymes, glutathione reductase 1, manganese superoxide dismutase (SOD), and Cu/Zn SOD remained unchanged. We suggest that salt-sensitive hypertension and behavioral derangement are associated with a redox imbalance in the brain of aged FBN rats.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aging*
  • Animals
  • Anxiety* / physiopathology
  • Blood Pressure
  • Corticosterone / blood
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / urine
  • Diet*
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Disease Models, Animal
  • Gene Expression Regulation
  • Glutathione Reductase / metabolism
  • Hypertension* / physiopathology
  • Lactoylglutathione Lyase / metabolism
  • Learning
  • Male
  • Memory, Short-Term*
  • Oxidative Stress
  • Rats
  • Sodium Chloride, Dietary / administration & dosage
  • Sodium Chloride, Dietary / adverse effects*
  • Superoxide Dismutase / metabolism


  • Sodium Chloride, Dietary
  • 8-epi-prostaglandin F2alpha
  • 8-Hydroxy-2'-Deoxyguanosine
  • Dinoprost
  • Superoxide Dismutase
  • Glutathione Reductase
  • Lactoylglutathione Lyase
  • Deoxyguanosine
  • Corticosterone