Lipoxygenase products regulate nitric oxide and inducible nitric oxide synthase production in interleukin-1beta stimulated vascular smooth muscle cells

Hypertens Res. 2003 Feb;26(2):177-84. doi: 10.1291/hypres.26.177.

Abstract

In cultured vascular smooth muscle cells (VSMCs), interleukin-1beta (IL-1beta) stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. IL-1beta also activates phospholipase A2 (PLA2), and induces lipoxygenase (LOX) and cyclooxygenase-2 (COX-2). The present study investigated whether these metabolites are involved in the regulation of IL-1beta-induced NO production and iNOS expression. Pretreatment with ONO-RS-082, the secretory PLA2 (sPLA2) inhibitor, at 1 to 10 micromol/l reduced IL-1beta-stimulated nitrite production and iNOS expression. Nordihydroguaiaretic acid (NDGA, 1 to 10 micromol/l), the LOX inhibitor, also reduced IL-1beta (10 ng/ml)-stimulated nitrite production and iNOS expression in a dose-dependent manner. Exogenous 12(S)-hydroxyeicosatetraenoic acids (HETE) enhanced the IL-1beta-stimulated nitrite production and iNOS expression. On the other hand, the COX inhibitors, indomethacin and NS-398, had little effect on nitrite production or iNOS expression. These results suggest that LOX products play important roles in the regulation of stimulus-induced NO production in VSMCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminobenzoates / pharmacology
  • Animals
  • Aorta, Thoracic / cytology
  • Cells, Cultured
  • Chlorobenzoates
  • Cinnamates / pharmacology
  • Cyclooxygenase Inhibitors / pharmacology
  • Flavanones*
  • Flavonoids / pharmacology
  • Group II Phospholipases A2
  • Interleukin-1 / pharmacology*
  • Lipoxygenase / metabolism*
  • Lipoxygenase Inhibitors / pharmacology
  • Male
  • Masoprocol / pharmacology
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / enzymology*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Phosphodiesterase Inhibitors / pharmacology
  • Phospholipases A / antagonists & inhibitors
  • Phospholipases A / metabolism
  • Phospholipases A2
  • Rats
  • Rats, Wistar
  • ortho-Aminobenzoates

Substances

  • Aminobenzoates
  • Chlorobenzoates
  • Cinnamates
  • Cyclooxygenase Inhibitors
  • Flavanones
  • Flavonoids
  • Interleukin-1
  • Lipoxygenase Inhibitors
  • Phosphodiesterase Inhibitors
  • ortho-Aminobenzoates
  • Nitric Oxide
  • baicalein
  • Masoprocol
  • 2-(4-amylcinnamoyl)amino-4-chlorobenzoic acid
  • Lipoxygenase
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Phospholipases A
  • Group II Phospholipases A2
  • Phospholipases A2