Aspirin inhibits NF-kappa B and protects from angiotensin II-induced organdamage

Angiotensin (Ang)-II induces vascular wall inflammation by activating NF-ka ppaB. Aspirin inhibits IKK beta 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-kappaB activation in v ivo. Rats harboring human renin and angiotensinogen genes received high- (6 00 mg/kg/day) or low- (25 mg/kg/day) dose aspirin. High-dose aspirin reduce d mortality, cardiac hypertrophy, fibrosis, and albuminuria independent of blood pressure, whereas both doses reduced cyclooxygenase activity. High-do se aspirin inhibited NF-kappaB and AP-1 activation and inflammation in hear t and kidney. These in vivo results serve to explain the clinical utility o f high- dose aspirin in inflammatory disorders and suggest additional thera peutic avenues that may be relevant to cardiovascular disease.