Hypertension. 2005;45:666-671
Published online before print February 7, 2005,
doi: 10.1161/01.HYP.0000153462.06604.5d
(Hypertension. 2005;45:666.)
© 2005 American Heart Association, Inc.
14,15-Epoxyeicosatrienoic Acid Represents a Transferable Endothelium-Dependent Relaxing Factor in Bovine Coronary Arteries
Kathryn M. Gauthier;
Erik M. Edwards;
John R. Falck;
Dendi S. Reddy;
William B. Campbell
From the Department of Pharmacology and Toxicology (K.M.G., E.M.E., W.B.C.), Medical College of Wisconsin, Milwaukee; and the Department of Biochemistry (J.R.F., D.S.R.), University of Texas Southwestern Medical School, Dallas.
Correspondence to Kathryn M. Gauthier, PhD, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. E-mail kgauth{at}mcw.edu
Bradykinin causes arterial relaxation and hyperpolarization, which is mediated by a transferable endothelium-derived hyperpolarizing factor (EDHF). In coronary arteries, epoxyeicosatrienoic acids (EETs) are involved in the EDHF response. However, the role of EETs as transferable mediators of EDHF-dependent relaxation remains poorly defined. Two small bovine coronary arteries were cannulated and perfused in tandem in the presence of the nitric oxide synthase inhibitor, nitro-L-arginine (30 µmol/L), and the cyclooxygenase inhibitor, indomethacin (10 µmol/L). Luminal perfusate from donor arteries with intact endothelium perfused endothelium-denuded detector arteries. Detector arteries were constricted with U46619 and diameters were monitored. Bradykinin (10 nmol/L) added to detector arteries did not induce dilation (5±2%), whereas bradykinin addition to donor arteries dilated detector arteries by 26.5±7% (P<0.05). These dilations were blocked by donor artery endothelium removal and detector artery treatment with the EET-selective antagonist, 14,15-epoxyeicosa-5(Z)-monoenoic acid (14,15-EEZE; 10 µmol/L, –5±6%) but not 14,15-EEZE treatment of donor arteries (20±5%). 14,15-EET (0.1 to 10 µmol/L) added to detector arteries induced maximal dilations of 82±5% that were inhibited 50% by detector artery treatment with 14,15-EEZE (32±12%) but not donor artery treatment with 14,15-EEZE. Liquid chromatography–electrospray ionization mass spectrometry analysis verified the presence of 14,15-EET in the perfusate from an endothelium-intact but not denuded artery. These results show that bradykinin stimulates donor artery 14,15-EET release that dilates detector arteries. 14,15-EEZE blocked the donor artery, endothelium-dependent, bradykinin-induced relaxations, and attenuated relaxations to 14,15-EET. These results suggest that EETs are transferable EDHFs in coronary arteries.
Key Words: bradykinin • endothelium-derived factors • vasodilation
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