PMID- 22526297
OWN - NLM
STAT- MEDLINE
DCOM- 20121228
LR  - 20211021
IS  - 1533-4023 (Electronic)
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 60
IP  - 1
DP  - 2012 Jul
TI  - Inhibition of soluble epoxide hydrolase limits niacin-induced vasodilation in 
      mice.
PG  - 70-5
LID - 10.1097/FJC.0b013e3182580a5d [doi]
AB  - BACKGROUND: The use of niacin in the treatment of dyslipidemias is limited by the 
      common side effect of cutaneous vasodilation, commonly termed flushing. Flushing 
      is thought to be due to release of the vasodilatory prostanoids prostaglandin D2 
      (PGD2) and prostaglandin E2 from arachidonic acid metabolism through the 
      cyclooxygenase pathway. Arachidonic acid is also metabolized by the cytochrome 
      P450 system, which is regulated, in part, by the enzyme soluble epoxide hydrolase 
      (sEH). METHODS: These experiments used an established murine model in which ear 
      tissue perfusion was measured by laser Doppler to test the hypothesis that 
      inhibition of sEH would limit niacin-induced flushing. RESULTS: Niacin-induced 
      flushing was reduced from 506 +/- 126% to 213 +/- 39% in sEH knockout animals. 
      Pharmacologic treatment with 3 structurally distinct sEH inhibitors similarly 
      reduced flushing in a dose-dependent manner, with maximal reduction to 143% +/- 15% 
      of baseline flow using a concentration of 1 mg/kg TPAU 
      (1-trifluoromethoxyphenyl-3-(1-acetylpiperidin-4-yl) urea). Systemically 
      administered PGD2 caused ear vasodilation, which was not changed by either 
      pharmacologic sEH inhibition or sEH gene deletion. CONCLUSIONS: Inhibition of sEH 
      markedly reduces niacin-induced flushing in this model without an apparent effect 
      on the response to PGD2. sEH inhibition may be a new therapeutic approach to 
      limit flushing in humans.
FAU - Inceoglu, Ahmet B
AU  - Inceoglu AB
AD  - Department of Entomology, University of California, Davis, CA, USA.
FAU - Clifton, Heather L
AU  - Clifton HL
FAU - Yang, Jun
AU  - Yang J
FAU - Hegedus, Christine
AU  - Hegedus C
FAU - Hammock, Bruce D
AU  - Hammock BD
FAU - Schaefer, Saul
AU  - Schaefer S
LA  - eng
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - R01 ES002710/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (1-trifluoromethoxyphenyl-3-(1-acetylpiperidin-4-yl)urea)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Piperidines)
RN  - 0 (Vasodilator Agents)
RN  - 2679MF687A (Niacin)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - RXY07S6CZ2 (Prostaglandin D2)
SB  - IM
MH  - Animals
MH  - Arachidonic Acid/metabolism
MH  - Dinoprostone/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Epoxide Hydrolases/genetics/*metabolism
MH  - Flushing/*chemically induced
MH  - Gene Deletion
MH  - Laser-Doppler Flowmetry
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Niacin/administration & dosage/*adverse effects/pharmacology
MH  - Phenylurea Compounds/pharmacology
MH  - Piperidines/pharmacology
MH  - Prostaglandin D2/administration & dosage/metabolism
MH  - Vasodilation/*drug effects
MH  - Vasodilator Agents/administration & dosage/adverse effects/pharmacology
PMC - PMC3396292
MID - NIHMS374162
EDAT- 2012/04/25 06:00
MHDA- 2012/12/29 06:00
PMCR- 2013/07/01
CRDT- 2012/04/25 06:00
PHST- 2012/04/25 06:00 [entrez]
PHST- 2012/04/25 06:00 [pubmed]
PHST- 2012/12/29 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - 10.1097/FJC.0b013e3182580a5d [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2012 Jul;60(1):70-5. doi: 10.1097/FJC.0b013e3182580a5d.