Sm. Klein et al., Effect of tyrosine kinase inhibition on sepsis-induced vascular hyporesponsiveness, iNOS mRNA expression and NF-kappa B nuclear translocation in rats, SHOCK, 14(5), 2000, pp. 544-549
Citations number
39
Categorie Soggetti
Aneshtesia & Intensive Care","Cardiovascular & Hematology Research
The dependence of the critical steps in the sepsis cascade on the transcrip
tion factor NF-kappaB and its relation to nitric oxide (NO) production are
controversial. Tyrosine kinase (TK) is involved in several of the steps, an
d TK inhibitors (TKI) inhibit lipopolysaccharide (LPS)-induced vascular hyp
oresponsiveness in septic animals. We studied the relationship of TK inhibi
tion, hemodynamics, vascular contraction, iNOS mRNA expression and NF-kappa
B translocation in anesthetized endotoxic rats. The TKI AG556 (2.5 mg/kg i.
p.), given 1 h before i.v. endotoxin (LPS) resulted in attenuation of early
(<60 min) and late (60-120 min) hypotension, improved contraction of mesen
teric arteries to norepinephrine 4 h after LPS, and attenuated tissue iNOS
mRNA expression. LPS-induced NF-<kappa>B translocation was unaffected. The
observed dissociation between NF-kappaB translocation and the salutary effe
ct of TKI in vivo and ex vivo and its effect on iNOS mRNA expression sugges
t that although NF-kappaB may be involved in the sepsis cascade, it may not
be essential for some of the molecular and vascular consequences of septic
shock.