Inhibition of nuclear factor-kappaB prevents the loss of vascular tone in lipopolysaccharide-treated rats.

We studied the role of nuclear factor-kappaB (NF-kappaB) on the tone and on the expression of inducible nitric oxide (NO) synthase, both evaluated in aortas from lipopolysaccharide-treated rats. Thoracic aorta rings from lipopolysaccharide-treated rats (4 mg/kg, i.p.), compared to those from naive animals, showed: (i) reduced contractility to phenylephrine, (ii) progressive loss in tone when contracted with phenylephrine, (iii) increased inducible NO synthase protein expression and NF-kappaB activation. Pyrrolidine dithiocarbamate (10, 30, 100 mg/kg, i.p.), an antioxidant inhibitor of NF-kappaB activation, dose dependently suppressed all these lipopolysaccharide-induced effects. These results demonstrate that in vivo inhibition of NF-kappaB activation prevented the lipopolysaccharide-induced loss of vascular tone, an effect which was correlated to reduced expression of inducible NO synthase protein.