PMID- 16258029
OWN - NLM
STAT- MEDLINE
DCOM- 20060228
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Linking)
VI  - 290
IP  - 2
DP  - 2006 Feb
TI  - Epoxyeicosatrienoic and dihydroxyeicosatrienoic acids dilate human coronary 
      arterioles via BK(Ca) channels: implications for soluble epoxide hydrolase 
      inhibition.
PG  - H491-9
AB  - Epoxyeicosatrienoic acids (EETs) are metabolized by soluble epoxide hydrolase 
      (sEH) to form dihydroxyeicosatrienoic acids (DHETs) and are putative 
      endothelium-derived hyperpolarizing factors (EDHFs). EDHFs modulate microvascular 
      tone; however, the chemical identity of EDHF in the human coronary 
      microcirculation is not known. We examined the capacity of EETs, DHETs, and sEH 
      inhibition to affect vasomotor tone in isolated human coronary arterioles (HCAs). 
      HCAs from right atrial appendages were prepared for videomicroscopy and 
      immunohistochemistry. In vessels preconstricted with endothelin-1, three EET 
      regioisomers (8,9-, 11,12-, and 14,15-EET) each induced a concentration-dependent 
      dilation that was sensitive to blockade of large-conductance Ca2+-activated K+ 
      (BK(Ca)) channels by iberiotoxin. EET-induced dilation was not altered by 
      endothelial denudation. 8,9-, 11,12-, and 14,15-DHET also dilated HCA via 
      activation of BK(Ca) channels. Dilation was less with 8,9- and 14,15-DHET but was 
      similar with 11,12-DHET, compared with the corresponding EETs. 
      Immunohistochemistry revealed prominent expression of cytochrome P-450 (CYP450) 
      2C8, 2C9, and 2J2, enzymes that may produce EETs, as well as sEH, in HCA. 
      Inhibition of sEH by 1-cyclohexyl-3-dodecylurea (CDU) enhanced dilation caused by 
      14,15-EET but reduced dilation observed with 11,12-EET. DHET production from 
      exogenous EETs was reduced in vessels pretreated with CDU compared with control, 
      as measured by liquid chromatography electrospray-ionization mass spectrometry. 
      In conclusion, EETs and DHETs dilate HCA by activating BK(Ca) channels, 
      supporting a role for EETs/DHETs as EDHFs in the human heart. CYP450s and sEH may 
      be endogenous sources of these compounds, and sEH inhibition has the potential to 
      alter myocardial perfusion, depending on which EETs are produced endogenously.
FAU - Larsen, Brandon T
AU  - Larsen BT
AD  - Department of Pharmacology and Toxicology, Medical College of Wisconsin, 
      Milwaukee, WI 53226, USA.
FAU - Miura, Hiroto
AU  - Miura H
FAU - Hatoum, Ossama A
AU  - Hatoum OA
FAU - Campbell, William B
AU  - Campbell WB
FAU - Hammock, Bruce D
AU  - Hammock BD
FAU - Zeldin, Darryl C
AU  - Zeldin DC
FAU - Falck, John R
AU  - Falck JR
FAU - Gutterman, David D
AU  - Gutterman DD
LA  - eng
GR  - R01 HL051055/HL/NHLBI NIH HHS/United States
GR  - F32 ES005707/ES/NIEHS NIH HHS/United States
GR  - HL-51055/HL/NHLBI NIH HHS/United States
GR  - DK-38266/DK/NIDDK NIH HHS/United States
GR  - R01 ES002710/ES/NIEHS NIH HHS/United States
GR  - P30 ES005707/ES/NIEHS NIH HHS/United States
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - Intramural NIH HHS/United States
GR  - ES-02710/ES/NIEHS NIH HHS/United States
GR  - HL-68769/HL/NHLBI NIH HHS/United States
GR  - ES-05707/ES/NIEHS NIH HHS/United States
GR  - ES-04699/ES/NIEHS NIH HHS/United States
GR  - P01 HL068769/HL/NHLBI NIH HHS/United States
GR  - R37 ES002710/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20051028
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Eicosanoids)
RN  - 0 (Large-Conductance Calcium-Activated Potassium Channels)
RN  - 0 (Vasodilator Agents)
RN  - EC 1.14.13.- (CYP2C9 protein, human)
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2C9)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP2C8 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C8)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Aged
MH  - Arterioles/drug effects/metabolism/*physiology
MH  - Aryl Hydrocarbon Hydroxylases/metabolism
MH  - Coronary Vessels/drug effects/metabolism/*physiology
MH  - Cytochrome P-450 CYP2C8
MH  - Cytochrome P-450 CYP2C9
MH  - Eicosanoids/metabolism/*pharmacology
MH  - Epoxide Hydrolases/antagonists & inhibitors/chemistry/metabolism
MH  - Female
MH  - Humans
MH  - In Vitro Techniques
MH  - Large-Conductance Calcium-Activated Potassium Channels/*physiology
MH  - Male
MH  - Middle Aged
MH  - Solubility
MH  - Vasodilation/*physiology
MH  - Vasodilator Agents/metabolism/*pharmacology
PMC - PMC1456013
MID - NIHMS9499
EDAT- 2005/11/01 09:00
MHDA- 2006/03/01 09:00
PMCR- 2008/02/01
CRDT- 2005/11/01 09:00
PHST- 2005/11/01 09:00 [pubmed]
PHST- 2006/03/01 09:00 [medline]
PHST- 2005/11/01 09:00 [entrez]
PHST- 2008/02/01 00:00 [pmc-release]
AID - 00927.2005 [pii]
AID - 10.1152/ajpheart.00927.2005 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2006 Feb;290(2):H491-9. doi: 
      10.1152/ajpheart.00927.2005. Epub 2005 Oct 28.