Extracorporeal shock waves: from lithotripsy to anti-inflammatory action by NO production

Nitric Oxide. 2005 Mar;12(2):89-96. doi: 10.1016/j.niox.2004.12.005.


At low energy density (0.03 mJ/mm2), extracorporeal shock waves (ESW), originally developed for clinical lithotripsy, have successfully been used for anti-inflammatory treatment of soft tissues. Since nitric oxide plays a critical role in inflammation, we hypothesized for ESW to increase NO production in cells. Using human umbilical vein endothelial cells as a model system, we observed that ESW, at low energy density, rapidly induced an enhancement of eNOS activity. In these cells, eNOS activity is modulated by tyrosine- and serine-phosphorylation. ESW shifted eNOS to a less-tyrosine-phosphorylated form, without affecting its serine-phosphorylation, thus accounting for its rapid enzyme activation. LPS/IFN-gamma treatment of human umbilical vein endothelial cells induced a rapid inhibition of eNOS activity and concomitant NF-kappaB activation which were efficiently counteracted by ESW treatment. Therefore, the present results indicate that the molecular mechanism of clinically observed anti-inflammatory action of ESW should include tyrosine-dephosphorylation of eNOS, a successive increase in NO production and suppression of NF-kappaB activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use*
  • Endothelium, Vascular / chemistry
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • High-Energy Shock Waves / therapeutic use*
  • Humans
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / pharmacology
  • Lithotripsy*
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type III
  • Phosphorylation
  • Serine / drug effects
  • Serine / metabolism
  • Tyrosine / drug effects
  • Tyrosine / metabolism


  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • NF-kappa B
  • Nitric Oxide
  • Tyrosine
  • Serine
  • Interferon-gamma
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III