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Role of the NF‐kB pathway in rats subjected to moderate hemorrhage
Author(s) -
Doursout MarieFrancoise Joelle,
Liang Yang Yan,
Uray Karen S.,
Pati Shibani,
Matijevic Nena,
Holcomb John B.
Publication year - 2009
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.23.1_supplement.lb380
Subject(s) - vasoconstriction , hemodynamics , medicine , shock (circulatory) , mean arterial pressure , hemorrhagic shock , blood volume , anesthesia , aorta , blood pressure , cardiac output , cardiology , heart rate
Mechanisms by which hemorrhagic shock leads to hemodynamic disturbances are not fully understood. Nuclear factor kB (NF‐kB) is a nuclear transcription factor that regulates expression of genes critical for the regulation of diseases. We hypothesize that NF‐kB is responsible for the hemodynamic changes associated with hemorrhagic shock in conscious rats. Under isoflurane, catheters were implanted into the aorta to record mean blood pressure (MAP) and heart rate (HR) and in the femoral vein for drug administrations. Cardiac output (CO) was recorded through Doppler flow probe. A blood volume of 2.0 ml/100 g of body weight was withdrawn over a 5‐min to induce moderate hemorrhage. Group 1 (n=6) was subjected to moderate hemorrhage only. Group 2 (n=5) was hemorrhaged in the presence of TPCK, an inhibitor of NF‐kB at 10 mg/kg sc. Our data show that hemorrhagic shock induced decreases in MAP by 30%, HR by 40% whereas CO remained unchanged. Moderate hemorrhage induced significant systemic vasoconstriction. As compared to hemorrhaged animals, TPCK restored MAP to baseline. Furthermore, moderate hemorrhage‐induced systemic vasoconstriction was significantly reduced in the presence of TPCK. Our data suggest that NF‐kB plays a major role in the hemodynamic changes induced by moderate hemorrhage. Development of NF‐kB inhibitors that will be tissue‐specific and/or isoform‐specific as therapeutic agents need to be pursued.