PMID- 22155238
OWN - NLM
STAT- MEDLINE
DCOM- 20120709
LR  - 20131121
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Linking)
VI  - 52
IP  - 3
DP  - 2012 Mar
TI  - Soluble epoxide hydrolase inhibition improves myocardial perfusion and function 
      in experimental heart failure.
PG  - 660-6
LID - 10.1016/j.yjmcc.2011.11.015 [doi]
AB  - The study addressed the hypothesis that soluble epoxide hydrolase (sEH) 
      inhibition, which increases cardiovascular protective epoxyeicosatrienoic acids 
      (EETs), exerts beneficial effects in an established chronic heart failure (CHF) 
      model. In CHF rats, left ventricular (LV) function, perfusion and remodeling were 
      assessed using MRI and invasive hemodynamics after 42-day (starting 8 days after 
      coronary ligation) and delayed 3-day (starting 47 days after coronary ligation) 
      treatments with the sEH inhibitor AUDA (twice 0.25 mg/day). Delayed 3-day and 
      42-day AUDA increased plasma EETs demonstrating the effective inhibition of sEH. 
      Delayed 3-day and 42-day AUDA enhanced cardiac output without change in arterial 
      pressure, thus reducing total peripheral resistance. Both treatment periods 
      increased the slope of the LV end-systolic pressure-volume relation, but only 
      42-day AUDA decreased LV end-diastolic pressure, relaxation constant Tau and the 
      slope of the LV end-diastolic pressure-volume relation, associated with a reduced 
      LV diastolic volume and collagen density. Delayed 3-day and, to a larger extent, 
      42-day AUDA increased LV perfusion associated with a decreased LV 
      hypoxia-inducible factor-1alpha. Both treatment periods decreased reactive oxygen 
      species level and increased reduced-oxidized glutathione ratio. Finally, MSPPOH, 
      an inhibitor of the EET-synthesizing enzyme cytochrome epoxygenases, abolished 
      the beneficial effects of 3-day AUDA on LV function and perfusion. Augmentation 
      of EET availability by pharmacological inhibition of sEH increases LV diastolic 
      and systolic functions in established CHF. This notably results from short-term 
      processes, i.e. increased LV perfusion, reduced LV oxidative stress and 
      peripheral vasodilatation, but also from long-term effects, i.e. reduced LV 
      remodeling.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Merabet, Nassiba
AU  - Merabet N
AD  - Institut National de la Sante et de la Recherche Medicale U644, University of 
      Rouen, Rouen, France.
FAU - Bellien, Jeremy
AU  - Bellien J
FAU - Glevarec, Etienne
AU  - Glevarec E
FAU - Nicol, Lionel
AU  - Nicol L
FAU - Lucas, Daniele
AU  - Lucas D
FAU - Remy-Jouet, Isabelle
AU  - Remy-Jouet I
FAU - Bounoure, Frederic
AU  - Bounoure F
FAU - Dreano, Yvonne
AU  - Dreano Y
FAU - Wecker, Didier
AU  - Wecker D
FAU - Thuillez, Christian
AU  - Thuillez C
FAU - Mulder, Paul
AU  - Mulder P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111206
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (12-(3-adamantan-1-ylureido)dodecanoic acid)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lauric Acids)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/administration & dosage/analogs & derivatives/pharmacology
MH  - Animals
MH  - *Coronary Circulation/drug effects
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/administration & dosage/pharmacology
MH  - Epoxide Hydrolases/*antagonists & inhibitors/metabolism
MH  - Heart Failure/drug therapy/*enzymology/*physiopathology
MH  - Hemodynamics/drug effects
MH  - Lauric Acids/administration & dosage/pharmacology
MH  - Male
MH  - Myocardial Infarction/drug therapy/enzymology/physiopathology
MH  - Myocardium/*enzymology
MH  - Nitric Oxide/metabolism
MH  - Oxidative Stress
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction
MH  - Ventricular Function, Left/drug effects
MH  - Ventricular Remodeling/drug effects
EDAT- 2011/12/14 06:00
MHDA- 2012/07/10 06:00
CRDT- 2011/12/14 06:00
PHST- 2011/06/17 00:00 [received]
PHST- 2011/11/18 00:00 [revised]
PHST- 2011/11/27 00:00 [accepted]
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2012/07/10 06:00 [medline]
AID - S0022-2828(11)00481-0 [pii]
AID - 10.1016/j.yjmcc.2011.11.015 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2012 Mar;52(3):660-6. doi: 10.1016/j.yjmcc.2011.11.015. Epub 
      2011 Dec 6.