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

SPECIFIC AIMSAspirin inhibits IKKβ in vitro; however, the in vivo relevance of the phenomenon is unclear. We have developed a model of severe angiotensin (Ang) II-induced vascular injury and now tested the hypothesis that chronic aspirin treatment of transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR) protects from Ang II-induced end organ damage by inhibiting NF-κB activation in vivo.PRINCIPAL FINDINGSHigh-dose aspirin reduces mortality and renal damage independent of blood pressureRenal glomerulus of untreated 7-wk-old dTGR shows mesangial expansion and podocyte damage. Renal dTGR arterioles exhibit severe changes in wall structure, including proliferation of smooth muscle cells and deposition of dense vacuoles. In contrast, nontransgenic Sprague-Dawley (SD) rats showed no vascular or glomerular damage. Untreated dTGR show signs of glomerular sclerosis and vascular damage with mortality > 50% at wk 7. High-dose aspirin reduced mortality to < 10% whereas low-dose aspirin produ...