Epoxyeicosatrienoic acids constrict isolated pressurized rabbit pulmonary arteries

Daling Zhu, Michael Bousamra, Darryl C. Zeldin, J R Falck, Mary Townsley, David R. Harder, Richard J. Roman, Elizabeth R. Jacobs

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Little information is available regarding the vasoactive effects of epoxyeicosatrienoic acids (EETs) in the lung. We demonstrate that 5,6-, 8,9- , 11,12-, and 14,15-EETs contract pressurized rabbit pulmonary arteries in a concentration-dependent manner. Constriction to 5,6-EET methyl ester or 14,15-EET is blocked by indomethacin or ibuprofen (10-5 M), SQ-29548, endothelial denuding, or submaximal preconstriction with the thromboxane mimetic U-46619. Constriction of pulmonary artery rings to phenylephrine is blunted by treatment with the epoxygenase inhibitor N-methylsulfonyl-6-(2- propargyloxyphenyl)hexanamide. Pulmonary arteries and peripheral lung microsomes metabolize arachidonate to products that comigrate on reverse- phrase HPLC with authentic regioisomers of 5,6-, 8,9-, 11,12-, and 14,15- EETs, but no cyclooxygenase products of EETs could be demonstrated. Proteins of the CYP2B, CYP2E, CYP2J, CYPIA, and CYP2C subfamilies are present in pulmonary artery and peripheral lung microsomes. Constriction of isolated rabbit pulmonary arteries to EETs is nonregioselective and depends on intact endothelium and cyclooxygenase, consistent with the formation of a pressor prostanoid compound. These data raise the possibility that EETs may contribute to regulation of pulmonary vascular tone.

Original languageEnglish (US)
Pages (from-to)L335-L343
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume278
Issue number2 22-2
DOIs
StatePublished - Feb 2000

Keywords

  • Arachidonic acid
  • Cytochrome P-450
  • Eicosanoid metabolism
  • Pulmonary vascular tone
  • Vasodilator

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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