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

Eur J Pharmacol. 1999 Jan 22;365(2-3):253-7. doi: 10.1016/s0014-2999(98)00888-7.

Abstract

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.

MeSH terms

  • Animals
  • In Vitro Techniques
  • Lipopolysaccharides / pharmacology*
  • Male
  • Muscle Relaxation / drug effects*
  • Muscle, Smooth, Vascular / drug effects*
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase Type II
  • Phenylephrine / pharmacology
  • Pyrrolidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Thiocarbamates / pharmacology*

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • Pyrrolidines
  • Thiocarbamates
  • Phenylephrine
  • pyrrolidine dithiocarbamic acid
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat