Ethyl Pyruvate Inhibits Hypoxic Pulmonary Vasoconstriction and Attenuates Pulmonary Artery Cytokine Expression

Ben M. Tsai, Tim Lahm, Eric D. Morrell, Paul R. Crisostomo, Jeffrey Poynter, Meijing Wang, Daniel R. Meldrum

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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% N2/5% CO2) with or without prior ethyl pyruvate (10 mm) treatment. Following 60 min of hypoxia, pulmonary artery rings were analyzed for tumor necrosis factor-α 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.

Original languageEnglish (US)
Pages (from-to)130-134
Number of pages5
JournalJournal of Surgical Research
Volume145
Issue number1
DOIs
StatePublished - Mar 1 2008

Keywords

  • hypoxia
  • inflammation
  • pulmonary hypertension
  • signal transduction

ASJC Scopus subject areas

  • Surgery

Fingerprint Dive into the research topics of 'Ethyl Pyruvate Inhibits Hypoxic Pulmonary Vasoconstriction and Attenuates Pulmonary Artery Cytokine Expression'. Together they form a unique fingerprint.

  • Cite this