PMID- 24691274
OWN - NLM
STAT- MEDLINE
DCOM- 20150724
LR  - 20220408
IS  - 1533-4023 (Electronic)
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 64
IP  - 1
DP  - 2014 Jul
TI  - An omega-3 epoxide of docosahexaenoic acid lowers blood pressure in 
      angiotensin-II-dependent hypertension.
PG  - 87-99
LID - 10.1097/FJC.0000000000000094 [doi]
AB  - Mediators of antihypertensive actions of docosahexaenoic acid (DHA) are largely 
      unknown. The omega-3 epoxide of DHA, 19, 20-EDP (epoxy docosapentaenoic acid), is 
      metabolized by soluble epoxide hydrolase (sEH), which also metabolizes the 
      anti-inflammatory and antihypertensive arachidonic acid epoxides, 
      epoxyeicosatrienoic acids (EETs). Based in part on plasma levels of EDPs after a 
      DHA-rich diet, we hypothesized that 19, 20-EDP contributes to the 
      antihypertensive actions of DHA in angiotensin-II (Ang-II)-dependent 
      hypertension. Treatment individually with 19, 20-EDP and a potent sEH inhibitor 
      TPPU (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea) significantly 
      lowered blood pressure (BP) as compared with Ang-II-infused animals. The largest 
      reduction in BP was obtained with the combination of 19, 20-EDP and TPPU, which 
      was more efficacious than the combination of 14, 15-EET and TPPU. Oxylipin 
      profiling revealed that 19, 20-EDP and 14, 15-EET infusion affected not only most 
      metabolites of the P450 pathway but also renal levels of prostaglandin-E2. Our 
      findings suggest that 19, 20-EDP is a mediator of the antihypertensive effects of 
      DHA in Ang-II-dependent hypertension. It seems that 19, 20-EDP requires metabolic 
      stabilization with a sEH inhibitor to be most effective in lowering BP, although 
      both TPPU and 19, 20-EDP are so effective on their own that demonstrating 
      additive or synergistic interactions is difficult.
FAU - Ulu, Arzu
AU  - Ulu A
AD  - *Department of Entomology and Comprehensive Cancer Center, University of 
      California, Davis, CA; and daggerSchool of Veterinary Medicine, Anatomy, Physiology 
      and Cell Biology, University of California, Davis, CA.
FAU - Stephen Lee, Kin Sing
AU  - Stephen Lee KS
FAU - Miyabe, Christina
AU  - Miyabe C
FAU - Yang, Jun
AU  - Yang J
FAU - Hammock, Bruce G
AU  - Hammock BG
FAU - Dong, Hua
AU  - Dong H
FAU - Hammock, Bruce D
AU  - Hammock BD
LA  - eng
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - R01 ES002710/ES/NIEHS NIH HHS/United States
GR  - U24 DK097154/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)urea)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Fatty Acids, Omega-3)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Piperidines)
RN  - 11128-99-7 (Angiotensin II)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Angiotensin II/metabolism
MH  - Animals
MH  - Antihypertensive Agents/*pharmacology
MH  - Blood Pressure/drug effects
MH  - Docosahexaenoic Acids/*pharmacology
MH  - Epoxide Hydrolases/metabolism
MH  - Fatty Acids, Omega-3/*pharmacology
MH  - Hypertension/*drug therapy/physiopathology
MH  - Male
MH  - Mice
MH  - Phenylurea Compounds/pharmacology
MH  - Piperidines/pharmacology
PMC - PMC4092041
MID - NIHMS571642
EDAT- 2014/04/03 06:00
MHDA- 2015/07/25 06:00
PMCR- 2015/07/01
CRDT- 2014/04/03 06:00
PHST- 2014/04/03 06:00 [entrez]
PHST- 2014/04/03 06:00 [pubmed]
PHST- 2015/07/25 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - 10.1097/FJC.0000000000000094 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2014 Jul;64(1):87-99. doi: 10.1097/FJC.0000000000000094.