Effect of soluble epoxide hydrolase inhibition on epoxyeicosatrienoic acid metabolism in human blood vessels

Xiang Fang, Neal L. Weintraub, Ryan B. McCaw, Shanming Hu, Shawn D. Harmon, James B. Rice, Bruce D. Hammock, Arthur A. Spector

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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 μmol/l 14, 15-[3H]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-[ 3H]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-[3H]EET to 11, 12-DHET by the HSV. sEH inhibition enhanced the uptake of 14, 15-[ 3H]EET and facilitated the formation of 10, 11-epoxy-16:2, a β-oxidation product. The HCA and HA converted 14, 15-[3H]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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number6 56-6
DOIs
StatePublished - Dec 2004
Externally publishedYes

Fingerprint

Epoxide Hydrolases
Blood Vessels
Saphenous Vein
Acids
Aorta
Urea
Coronary Vessels
Adventitia
Radioactivity
Endothelium
14,15-dihydroxyeicosatrienoic acid
Perfusion
14,15-epoxy-5,8,11-eicosatrienoic acid

Keywords

  • β-oxidation
  • Cytochrome P-450
  • Dihydroxyeicosatrienoic acids
  • Saphenous vein

ASJC Scopus subject areas

  • Physiology

Cite this

Effect of soluble epoxide hydrolase inhibition on epoxyeicosatrienoic acid metabolism in human blood vessels. / Fang, Xiang; Weintraub, Neal L.; McCaw, Ryan B.; Hu, Shanming; Harmon, Shawn D.; Rice, James B.; Hammock, Bruce D.; Spector, Arthur A.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 287, No. 6 56-6, 12.2004.

Research output: Contribution to journalArticle

Fang, Xiang ; Weintraub, Neal L. ; McCaw, Ryan B. ; Hu, Shanming ; Harmon, Shawn D. ; Rice, James B. ; Hammock, Bruce D. ; Spector, Arthur A. / Effect of soluble epoxide hydrolase inhibition on epoxyeicosatrienoic acid metabolism in human blood vessels. In: American Journal of Physiology - Heart and Circulatory Physiology. 2004 ; Vol. 287, No. 6 56-6.
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AU - Fang, Xiang

AU - Weintraub, Neal L.

AU - McCaw, Ryan B.

AU - Hu, Shanming

AU - Harmon, Shawn D.

AU - Rice, James B.

AU - Hammock, Bruce D.

AU - Spector, Arthur A.

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N2 - 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 μmol/l 14, 15-[3H]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-[ 3H]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-[3H]EET to 11, 12-DHET by the HSV. sEH inhibition enhanced the uptake of 14, 15-[ 3H]EET and facilitated the formation of 10, 11-epoxy-16:2, a β-oxidation product. The HCA and HA converted 14, 15-[3H]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.

AB - 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 μmol/l 14, 15-[3H]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-[ 3H]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-[3H]EET to 11, 12-DHET by the HSV. sEH inhibition enhanced the uptake of 14, 15-[ 3H]EET and facilitated the formation of 10, 11-epoxy-16:2, a β-oxidation product. The HCA and HA converted 14, 15-[3H]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.

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KW - Saphenous vein

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