Acetylsalicylic acid provides cerebrovascular protection from oxidant damage in salt-loaded stroke-prone rats.

Abstract

Inflammatory processes may play a pivotal role in the pathogenesis of cerebrovascular injury in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Recent reports revealed that acetylsalicylic acid (aspirin) has anti-oxidative properties and elicits nitric oxide release by a direct activation of the endothelial NO synthase. The present study was designed to determine whether low-dose aspirin might prevent cerebrovascular injury in salt-loaded SHRSP by protecting oxidative damage. Nine-week-old SHRSP were fed a 0.4% NaCl or a 4% NaCl diet with or without treatment by naproxen (20 mg/kg/day), salicylic acid (5 mg/kg/day), or aspirin (5 mg/kg/day) for 5 weeks. Blood pressure, blood brain barrier impairment, mortality, and the parameters of cerebrovascular inflammation and damage were compared among them. High salt intake in SHRSP significantly increased blood brain barrier impairment and early mortality, which were suppressed by treatment with aspirin independent of changes in blood pressure. Salt loading significantly increased superoxide production in basilar arteries of SHRSP, which were significantly suppressed by treatment with aspirin. Salt loading also significantly decreased NOS activity in the basilar arteries of SHRSP, which were significantly improved by treatment with aspirin. At 5 weeks after salt loading, macrophage accumulation and matrix metalloproteinase-9 activity at the stroke-negative area in cerebral cortex of SHRSP were significantly reduced by treatment with aspirin. These results suggest that low-dose aspirin may exert protective effects against cerebrovascular inflammation and damage by salt loading through down-regulation of superoxide production and induction of nitric oxide synthesis.

• Authors: Toshiaki Ishizuka, Atsuko Niwa, Masaki Tabuchi, Kana Ooshima, Hideaki Higashino
• Journal: Life sciences (Life Sci) Vol. 82 Issue 13-14 Pg. 806-15 (Mar 26 2008) ISSN: 0024-3205 [Print] Netherlands
• PMID: 18313079 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Sodium Chloride, Dietary
• Superoxides
• Nitric Oxide Synthase
• Aspirin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Aspirin (pharmacology, therapeutic use)
• Basilar Artery (drug effects, enzymology, metabolism)
• Blood Pressure (drug effects)
• Blood-Brain Barrier (drug effects, metabolism, pathology)
• Male
• Nitric Oxide Synthase (metabolism)
• Oxidative Stress (drug effects)
• Rats
• Rats, Inbred Strains
• Sodium Chloride, Dietary (administration & dosage)
• Stroke (metabolism, physiopathology, prevention & control)
• Superoxides (metabolism)