Faculty Collaboration Database

14,15-epoxyeicosatrienoic acid represents a transferable endothelium-dependent relaxing factor in bovine coronary arteries. Hypertension 2005 Apr;45(4):666-71

Date

02/09/2005

Pubmed ID

15699460

DOI

10.1161/01.HYP.0000153462.06604.5d

Scopus ID

2-s2.0-15744364647 (requires institutional sign-in at Scopus site)   67 Citations

Abstract

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 micromol/L), and the cyclooxygenase inhibitor, indomethacin (10 micromol/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 micromol/L, -5+/-6%) but not 14,15-EEZE treatment of donor arteries (20+/-5%). 14,15-EET (0.1 to 10 micromol/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.

Author List

Gauthier KM, Edwards EM, Falck JR, Reddy DS, Campbell WB

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

8,11,14-Eicosatrienoic Acid
Animals
Biological Assay
Bradykinin
Cattle
Coronary Vessels
Endothelium, Vascular
Endothelium-Dependent Relaxing Factors
In Vitro Techniques
Muscle, Smooth, Vascular
Vasodilation