Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 287, Issue 6, Pages H2412-H2420Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00527.2004
Keywords
dihydroxyeicosatrienoic acids; cytochrome P-450; saphenous vein; beta-oxidation
Funding
- NHLBI NIH HHS [HL-070860, HL-49264, HL-72845, HL-62984, R01 HL-59699-06A1] Funding Source: Medline
- NIEHS NIH HHS [P30 ES-05707, P01 ES-11269-01, ES-02710, P42 ES-04699] Funding Source: Medline
Ask authors/readers for more resources
We investigated the effects of soluble epoxide hydrolase (sEH) inhibition on epoxyeicosatrienoic acid (EET) metabolism in intact human blood vessels, including the human saphenous vein (HSV), coronary artery (HCA), and aorta (HA). When HSV segments were perfused with 2 mumol/l 14,15-[H-3] EET for 4 h, >60% of radioactivity in the perfusion medium was converted to 14,15- dihydroxyeicosatrienoic acid (DHET). Similar results were obtained with endothelium-denuded vessels. 14,15- DHET was released from both the luminal and adventitial surfaces of the HSV. When HSVs were incubated with 14,15-[H-3] EET under static (no flow) conditions, formation of 14,15-DHET was detected within 15 min and was inhibited by the selective sEH inhibitors N,N'-dicyclohexyl urea and N-cyclohexyl-N'-dodecanoic acid urea (CUDA). Similarly, CUDA inhibited the conversion of 11,12-[H-3] EET to 11,12- DHET by the HSV. sEH inhibition enhanced the uptake of 14,15-[H-3] EET and facilitated the formation of 10,11-epoxy-16:2, a beta-oxidation product. The HCA and HA converted 14,15-[H-3] EET to DHET, and this also was inhibited by CUDA. These findings in intact human blood vessels indicate that conversion to DHET is the predominant pathway for 11,12- and 14,15-EET metabolism and that sEH inhibition can modulate EET metabolism in vascular tissue.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available