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Aspirin inhibits NF‐κB and protects from angiotensin II‐induced organ damage
Author(s) -
Muller Dominik N.,
Heissmeyer Vigo,
Dechend Ralf,
Hampich Franziska,
Park Joon-Keun,
Fiebeler Anette,
Shagdarsuren Erdenechimeg,
Theuer Jürgen,
Elger Marlies,
Pilz Bernhard,
Breu Volker,
Schroer Karsten,
Ganten Detlev,
Dietz Rainer,
Haller Hermann,
Scheidereit Claus,
Luft Friedrich C.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0843fje
Subject(s) - aspirin , angiotensin ii , medicine , pharmacology , nf κb , renin–angiotensin system , chemistry , inflammation , receptor , blood pressure
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.