Epoxyeicosatrienoic acids increase intracellular calcium concentration in vascular smooth muscle cells

Xiang Fang, Neal L. Weintraub, Lynn L. Stoll, Arthur A. Spector

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Epoxyeicosatrienoic acids (EETs) are cytochrome P450-derived metabolites of arachidonic acid. They are potent endogenous vasodilator compounds produced by vascular cells, and EET-induced vasodilation has been attributed to activation of vascular smooth muscle cell (SMC) K+ channels. However, in some cells, EETs activate Ca2+ channels, resulting in Ca2+ influx and increased intracellular Ca2+ concentration ([Ca2+](i)). We investigated whether EETs also can activate Ca2+ channels in vascular SMC and whether the resultant Ca2+ influx can influence vascular tone. The 4 EET regioisomers (1 μmol/L) increased-porcine aortic SMC [Ca2+](i) by 52% to 81%, whereas arachidonic acid, dihydroxyeicosatrienoic acids, and 15- hydroxyeicosatetraenoic acid (1 μmol/L) produced little effect. The increases in [Ca2+](i) produced by 14,15-EET were abolished by removal of extracellular Ca2+ and by pretreatment with verapamil (10 μmol/L), an inhibitor of voltage-dependent (L-type) Ca2+ channels. 14,15-EET did not alter Ca2+ signaling induced by norepinephrine and thapsigargin. When administered to porcine coronary artery rings precontracted with a thromboxane mimetic, 14,15-EET produced relaxation. However, when administered to rings precontracted with acetylcholine or KCl, 14,15-EET produced additional contractions. In rings exposed to 10 mmol/L KCl, a concentration that did not affect resting ring tension, 14,15-EET produced small contractions that were abolished by EGTA (3 mmol/L) or verapamil (10 μmol/L). These observations indicate that 14,15-EET enhances [Ca2+](i) influx in vascular SMC through voltage-dependent Ca2+ channels. This 14,15- EET-induced increase in [Ca(i)2+] can produce vasoconstriction and therefore may act to modulate EET-induced vasorelaxation.

Original languageEnglish (US)
Pages (from-to)1242-1246
Number of pages5
JournalHypertension
Volume34
Issue number6
StatePublished - Dec 1999
Externally publishedYes

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Keywords

  • Calcium channels
  • Endothelium-derived factor
  • Epoxyeicosatrienoic acid
  • Vasoconstriction
  • Vasorelaxation

ASJC Scopus subject areas

  • Internal Medicine

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