Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor

Nature. 1986 Apr 3-9;320(6061):454-6. doi: 10.1038/320454a0.

Abstract

Endothelium-derived vascular relaxing factor (EDRF) is a humoral agent that is released by vascular endothelium and mediates vasodilator responses induced by various substances including acetylcholine and bradykinin. EDRF is very unstable, with a half-life of between 6 and 50 s, and is clearly distinguishable from prostacyclin. The chemical structure of EDRF is unknown but it has been suggested that it is either a hydroperoxy- or free radical-derivative of arachidonic acid or an unstable aldehyde, ketone or lactone. We have examined the role of superoxide anion (O-2) in the inactivation of EDRF released from vascular endothelial cells cultured on microcarrier beads and bioassayed using a cascade of superfused aortic smooth muscle strips. With this system, we have now demonstrated that EDRF is protected from breakdown by superoxide dismutase (SOD) and Cu2+, but not by catalase, and is inactivated by Fe2+. These findings indicate that O-2 contributes significantly to the instability of EDRF.

MeSH terms

  • Animals
  • Bradykinin / pharmacology
  • Catalase / metabolism
  • Copper / metabolism
  • Endothelium / physiology*
  • Iron / metabolism
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Nitric Oxide
  • Rabbits
  • Superoxide Dismutase / metabolism
  • Superoxides / physiology*
  • Vasodilator Agents / metabolism*

Substances

  • Vasodilator Agents
  • Superoxides
  • Nitric Oxide
  • Copper
  • Iron
  • Catalase
  • Superoxide Dismutase
  • Bradykinin