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Hypertension. 1999;34:1242-1246

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(Hypertension. 1999;34:1242.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Epoxyeicosatrienoic Acids Increase Intracellular Calcium Concentration in Vascular Smooth Muscle Cells

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

From the Departments of Biochemistry (X.F., A.A.S.) and Internal Medicine (N.L.W., L.L.S., A.A.S.), University of Iowa College of Medicine, Iowa City.

Correspondence to Xiang Fang, MD, PhD, Department of Biochemistry, University of Iowa, Iowa City, IA 52242. E-mail xiang-fang{at}uiowa.edu

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 [Cai2+] can produce vasoconstriction and therefore may act to modulate EET-induced vasorelaxation.


Key Words: calcium channels • epoxyeicosatrienoic acid • endothelium-derived factor • vasoconstriction • vasorelaxation




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