14,15-Dihydroxyeicosatrienoic acid relaxes bovine coronary arteries by activation of K(Ca) channels. Am J Physiol Heart Circ Physiol 2002 May;282(5):H1656-64
Date
04/18/2002Pubmed ID
11959628DOI
10.1152/ajpheart.00597.2001Scopus ID
2-s2.0-0036089541 (requires institutional sign-in at Scopus site) 59 CitationsAbstract
Epoxyeicosatrienoic acids (EETs) cause vascular relaxation by activating smooth muscle large conductance Ca(2+)-activated K(+) (K(Ca)) channels. EETs are metabolized to dihydroxyeicosatrienoic acids (DHETs) by epoxide hydrolase. We examined the contribution of 14,15-DHET to 14,15-EET-induced relaxations and characterized its mechanism of action. 14,15-DHET relaxed U-46619-precontracted bovine coronary artery rings but was approximately fivefold less potent than 14,15-EET. The relaxations were inhibited by charybdotoxin, iberiotoxin, and increasing extracellular K(+) to 20 mM. In isolated smooth muscle cells, 14,15-DHET increased an iberiotoxin-sensitive, outward K(+) current and increased K(Ca) channel activity in cell-attached patches and inside-out patches only when GTP was present. 14,15-[(14)C]EET methyl ester (Me) was converted to 14,15-[(14)C]DHET-Me, 14,15-[(14)C]DHET, and 14,15-[(14)C]EET by coronary arterial rings and endothelial cells but not by smooth muscle cells. The metabolism to 14,15-DHET was inhibited by the epoxide hydrolase inhibitors 4-phenylchalcone oxide (4-PCO) and BIRD-0826. Neither inhibitor altered relaxations to acetylcholine, whereas relaxations to 14,15-EET-Me were increased slightly by BIRD-0826 but not by 4-PCO. 14,15-DHET relaxes coronary arteries through activation of K(Ca) channels. Endothelial cells, but not smooth muscle cells, convert EETs to DHETs, and this conversion results in a loss of vasodilator activity.
Author List
Campbell WB, Deeter C, Gauthier KM, Ingraham RH, Falck JR, Li PLAuthor
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid8,11,14-Eicosatrienoic Acid
Acetylcholine
Animals
Calcium
Cattle
Charybdotoxin
Coronary Vessels
Electric Conductivity
Endothelium, Vascular
Enzyme Inhibitors
Epoxide Hydrolases
GTP-Binding Proteins
Guanosine Triphosphate
Hydroxyeicosatetraenoic Acids
Muscle Relaxation
Muscle, Smooth, Vascular
Peptides
Potassium Channels
