20-Hydroxyeicosatetraenoic acid is a vasoconstrictor in the newborn piglet pulmonary microcirculation

Mamta Fuloria, Delrae M. Eckman, Daniel A. Leach, Judy L. Aschner

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

20-Hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P-450 metabolite of arachidonic acid, is a vasoconstrictor in the systemic circulation and a vasodilator in the adult pulmonary circulation. Little is known about the vasoactive properties of 20-HETE in the newborn pulmonary circulation. The objectives of this study were to determine the vascular effects of 20-HETE and to explore the signaling mechanism(s) that mediate these effects in newborn pulmonary resistance-level arteries (PRA). Our findings demonstrate that, in contrast to the adult pulmonary circulation where 20-HETE mediates vasodilation, it causes constriction in newborn PRA at resting tone. Furthermore, inhibition of cyclooxygenase (COX) with indomethacin augments 20-HETE-induced constriction. The enhanced constrictor response to 20-HETE under conditions of COX inhibition is abolished in endothelium-disrupted PRA, suggesting that 20-HETE either stimulates endothelium-derived COX to release a counteracting vasodilator or is rapidly metabolized by COX to a less potent vasoconstrictor. 20-HETE-induced constriction is significantly inhibited by blocking calcium-dependent K + (KCa) channels and the thromboxane-PGH2 receptor. Altogether, our data indicate that the vascular actions of 20-HETE are partially mediated via the activation of KCa channels and are significantly modulated by interactions with the COX-prostaglandin pathway.

Original languageEnglish (US)
Pages (from-to)L360-L365
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume287
Issue number2 31-2
DOIs
Publication statusPublished - Aug 1 2004

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Keywords

  • Calcium-dependent channels
  • Cyclooxygenase
  • Cytochrome P-450
  • Pulmonary resistance arteries
  • Thromboxane-PGH receptor

ASJC Scopus subject areas

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

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