Premium
Different pathways in LPS and TNF ‐αinduced iNOS expression in arteries and veins in septic shock rats
Author(s) -
Xu Hui
Publication year - 2010
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/fasebj.24.1_supplement.788.6
Subject(s) - tumor necrosis factor alpha , adventitia , lipopolysaccharide , receptor , septic shock , mesenteric arteries , chemistry , endocrinology , inflammation , medicine , nf κb , signal transduction , sepsis , artery , biochemistry
We have shown that mesenteric arteries (MA) and veins (MV) are hyporeactive to NE after in vitro and in vivo LPS treatment, but the mechanisms are different. MV are resistant to LPS‐induced dysfunction but are sensitive to TNF‐α while MA function is disrupted by LPS but not TNF‐α. LPS‐activated inflammatory signaling pathways are not functional in MV. TNF‐R1 is the primary receptor for TNF‐α‐induced inflammatory responses in blood vessels. Activation of Toll‐like receptors by LPS and TNF‐α induce different signal pathways, but both pathways activate NFκB to induce iNOS expression and activation of iNOS. iNOS‐induced NO contributes to vascular hyporeactivity in septic shock. Therefore, it is crucial to determine if there is different expression of TNF‐R1, and NFκB‐induced iNOS in MA and MV. MA and MV were taken from control and hypotensive rats that were treated 6–8 hours previously with LPS (10 mg/kg, ip, n=4). TNF‐R1 and iNOS expression were measured using immunohistochemistry. TNF‐R1 was equally expressed in endothelial cells (EC), smooth muscle cells (SMC), and in the adventitia of MA and MV from control and LPS‐treated rats. iNOS was only expressed in EC and adventitia in MA and MV from control rats. iNOS expression was significantly increased in SMC in MA and MV from LPS‐treated rats. These data indicated that TNF‐R1 does not contribute to TNF‐α‐resistance in MA. Pathways downstream from NFκB are equally functional in MA and MV. Toll‐like receptors and TNF‐R1‐induced signal transduction to activation of NFκB need to be studied.