Role of 5,6-epoxyeicosatrienoic acid in the regulation of newborn piglet pulmonary vascular tone

Mamta Fuloria, Thuy K. Smith, Judy L. Aschner

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

We examined the responses of newborn piglet pulmonary resistance arteries (PRAs) to 5,6-epoxyeicosatrienoic acid (5,6-EET), a cytochrome P-450 metabolite of arachidonic acid. In PRAs preconstricted with a thromboxane A2 mimetic, 5,6-EET caused a concentration-dependent dilation. This dilation was partially inhibited by the combination of charybdotoxin (CTX) and apamin, inhibitors of large and small conductance calcium-dependent potassium (KCa) channels, and was abolished by depolarization of vascular smooth muscle with KCl. Disruption of the endothelium significantly attenuated the dilation, suggesting involvement of one or more endothelium-derived vasodilator pathways in this response. The dilation was partially inhibited by nitro-L-arginine (L-NA), an inhibitor of nitric oxide synthase (NOS), but was unaffected by indomethacin, a cyclooxygenase (COX) inhibitor. The combined inhibition of NOS and KCa channels with L-NA, CTX, and apamin abolished 5,6-EET-mediated dilation. Similarly, combined inhibition of NOS and COX abolished the response. We conclude that 5,6-EET is a potent vasodilator in newborn piglet PRAs. This dilation is mediated by redundant pathways that include release of nitric oxide (NO) and COX metabolites and activation of KCa channels. The endothelium dependence of this response suggests that 5,6-EET is not itself an endothelium-derived hyperpolarizing factor (EDHF) but may induce the release of one or more endothelium-derived relaxing factors, such as NO and/or EDHF.

Original languageEnglish (US)
Pages (from-to)L383-L389
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number2 27-2
DOIs
StatePublished - Jan 1 2002

Keywords

  • Calcium-dependent potassium channels
  • Endothelium-derived hyperpolarizing factor
  • Nitric oxide
  • Pulmonary resistance arteries

ASJC Scopus subject areas

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

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