TY - JOUR
T1 - 14,15-Epoxyeicosatrienoic acid represents a transferable endothelium-dependent relaxing factor in bovine coronary arteries
AU - Gauthier, Kathryn M.
AU - Edwards, Erik M.
AU - Falck, John R.
AU - Reddy, Dendi S.
AU - Campbell, William B.
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
KW - Bradykinin
KW - Endothelium-derived factors
KW - Vasodilation
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U2 - 10.1161/01.HYP.0000153462.06604.5d
DO - 10.1161/01.HYP.0000153462.06604.5d
M3 - Article
C2 - 15699460
AN - SCOPUS:15744364647
SN - 0194-911X
VL - 45
SP - 666
EP - 671
JO - Hypertension
JF - Hypertension
IS - 4 SUPPL.
ER -