BACKGROUND: In acute @entity1457 , a rapid systemic release of the inflammatory cytokine tumor @entity39 factor ( @entity1505 ) contributes to vascular failure. Nuclear factor kappaB (NF-kappaB) is an ubiquitous rapid-response transcription factor involved in inflammatory reactions and exerts its effect by expressing cytokines, chemokines, and cell adhesion molecules. The purpose of this study was to evaluate the role of NF-kappaB in acute @entity548 . METHODS: @entity548 was induced in anesthetized male @entity35 by intermittently withdrawing blood from an iliac catheter for 20 minutes (bleeding period) until mean arterial blood pressure (MAP) decreased and stabilized within the range of 20 to 30 mm Hg. Two minutes after bleeding was discontinued the @entity35 received @entity1140 (100 microg/kg), an inhibitor of NF-kappaB activation, or its vehicle. We then evaluated survival rate and survival time, liver NF-kappaB activation by means of electrophoretic mobility shift assay, liver @entity24317 protein in the cytoplasm, hepatic @entity1505 messenger RNA expression, plasma @entity1505 , arterial blood pressure, and the contractile response of aortic rings to @entity2647 . RESULTS: @entity35 that underwent @entity548 died 28+/-2 minutes after bleeding was discontinued, experienced marked @entity551 (MAP, 20-30 mm Hg), and had enhanced plasma levels of @entity1505 (218 +/- 28 pg/mL 20 minutes after bleeding was discontinued). Aortas taken 20 minutes after bleeding was discontinued in @entity35 that underwent @entity548 showed marked hyporeactivity to @entity2647 (1 nmol/L-10 micromol/L) compared with aortas harvested from sham shocked @entity35 . @entity35 that underwent @entity548 also had increased levels of @entity1505 messenger RNA in the liver. Furthermore, electrophoretic mobility shift assay showed that liver NF-kappaB binding activity increased in the nucleus, and Western blot analysis suggested that the levels of inhibitory @entity24317 protein in the cytoplasm decreased. @entity1140 (100 microg/kg, administered 2 minutes after bleeding was discontinued) inhibited the loss of @entity24317 protein from the cytoplasm and prevented NF-kappaB binding activity in the nucleus. Moreover, @entity1140 increased survival time (118 +/- 7 minutes; P <.01) and survival rate (vehicle = 0 and @entity1140 = 90% 240 minutes after bleeding was discontinued), reverted the marked @entity551 , decreased liver messenger RNA for @entity1505 reduced plasma @entity1505 (35 +/- 6 pg/mL), and restored the hyporeactivity to @entity2647 to control values. CONCLUSIONS: Our results suggest that @entity190 (50% of the estimated total blood volume during a 20-minute period) causes activation of NF-kappaB and that @entity1140 , by inhibiting this transcription factor, protects against acute @entity1457 .

Evidence for a role of nuclear factor-kappaB in acute XXXX .

@entity548 :: ('MESH:D006470', 'Disease') :: ['hypovolemic hemorrhagic shock', 'Hemorrhagic shock', 'hemorrhagic shock'] @entity39 :: ('MESH:D009336', 'Disease') :: ['necrosis'] @entity190 :: ('MESH:D006473', 'Disease') :: ['acute blood loss'] @entity1457 :: ('MESH:D012769', 'Disease') :: ['hypovolemic shock'] @entity1505 :: ('24835(Tax:10116)', 'Gene') :: ['TNF-alpha'] @entity2647 :: ('MESH:D010656', 'Chemical') :: ['phenylephrine'] @entity24317 :: ('25493(Tax:10116)', 'Gene') :: ['IkappaBalpha'] @entity1140 :: ('MESH:D016559', 'Chemical') :: ['Tacrolimus', 'tacrolimus'] @entity35 :: ('10116', 'Species') :: ['Rats', 'rats'] @entity551 :: ('MESH:D007022', 'Disease') :: ['hypotension']
@entity548 :: (MESH:D006470,Disease) :: ['hypovolemic hemorrhagic shock']
