Ethyl pyruvate inhibits hypoxic pulmonary vasoconstriction and attenuates pulmonary artery cytokine expression

J Surg Res. 2008 Mar;145(1):130-4. doi: 10.1016/j.jss.2007.03.067. Epub 2007 Jun 14.


Hypoxic pulmonary vasoconstriction is a common consequence of acute lung injury and may be mediated by increased local production of proinflammatory cytokines. Ethyl pyruvate is a novel anti-inflammatory agent that has been shown to down-regulate proinflammatory genes following hemorrhagic shock; however, its effects on hypoxic pulmonary vasoconstriction are unknown. We hypothesized that ethyl pyruvate would inhibit hypoxic pulmonary vasoconstriction and down-regulate pulmonary artery cytokine expression during hypoxia. To study this, isometric force displacement was measured in isolated rat pulmonary artery rings (n = 8/group) during hypoxia (95% N(2)/5% CO(2)) with or without prior ethyl pyruvate (10 mm) treatment. Following 60 min of hypoxia, pulmonary artery rings were analyzed for tumor necrosis factor-alpha and interleukin-1 mRNA via reverse transcriptase polymerase chain reaction. Ethyl pyruvate inhibited hypoxic pulmonary artery contraction (4.49 +/- 2.32% versus 88.80 +/- 5.68% hypoxia alone) and attenuated the hypoxic up-regulation of pulmonary artery tumor necrosis factor and interleukin-1 mRNA (P < 0.05). These data indicate that (1) hypoxia increases pulmonary artery vasoconstriction and proinflammatory cytokine gene expression; (2) ethyl pyruvate decreases hypoxic pulmonary vasoconstriction and down-regulates hypoxia-induced pulmonary artery proinflammatory cytokine gene expression; and (3) ethyl pyruvate may represent a novel therapeutic adjunct in the treatment of acute lung injury.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Hypoxia / metabolism
  • Hypoxia / physiopathology
  • Hypoxia / prevention & control*
  • Interleukin-1 / metabolism
  • Lung / blood supply
  • Lung / metabolism*
  • Male
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / physiopathology
  • Pyruvates / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • Vasoconstriction / drug effects*


  • Anti-Inflammatory Agents
  • Cytokines
  • Interleukin-1
  • Pyruvates
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • ethyl pyruvate