Aspirin inhibits NF‐κB and protects from angiotensin II‐induced organ damage

Angiotensin (Ang)‐II induces vascular wall inflammation by activating NF‐κB. Aspirin inhibits IKKβ in vitro; however, the in vivo relevance of the phenomenon is unclear. We tested the hypothesis that aspirin protects from Ang II‐induced endorgan damage by inhibiting NF‐κB activation in vivo. Rats harboring human renin and angiotensinogen genes received high‐ (600 mg/kg/day) or low‐ (25 mg/kg/day) dose aspirin. High‐dose aspirin reduced mortality, cardiac hypertrophy, fibrosis, and albuminuria independent of blood pressure, whereas both doses reduced cyclooxygenase activity. High‐dose aspirin inhibited NF‐κB and AP‐1 activation and inflammation in heart and kidney. These in vivo results serve to explain the clinical utility of high‐dose aspirin in inflammatory disorders and suggest additional therapeutic avenues that may be relevant to cardiovascular disease.