PMID- 14578116
OWN - NLM
STAT- MEDLINE
DCOM- 20040304
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 286
IP  - 2
DP  - 2004 Feb
TI  - Role of EETs in regulation of endothelial permeability in rat lung.
PG  - L445-51
AB  - This study tested the hypothesis that epoxyeicosatrienoic acids (EETs) derived 
      from arachidonic acid via P-450 epoxygenases are soluble factors linking 
      depletion of endoplasmic reticulum Ca(2+) stores and store-dependent regulation 
      of endothelial cell (EC) permeability in rat lung. EC permeability was measured 
      via the capillary filtration coefficient (K(f,c)) in isolated, perfused rat 
      lungs. 14,15-EET and 5,6-EET increased EC permeability, a response that was 
      significantly different from that of 8,9-EET, 11,12-EET, and vehicle control. The 
      permeability response to 14,15-EET was not significantly attenuated by the 
      nonspecific Ca(2+) channel blocker Gd(3+) (P = 0.068). In lungs perfused with low 
      [Ca(2+)], 14,15-EET tended to increase EC permeability, although a significant 
      increase in K(f,c) was observed only following Ca(2+) add-back. As positive 
      control, we showed that the 3.7-fold increase in K(f,c) evoked by thapsigargin 
      (TG), a known activator of store depletion-induced Ca(2+) entry, was blocked by 
      both Gd(3+) and low [Ca(2+)] buffer. Nonetheless, the permeability response to TG 
      could not be blocked by the phospholipase A(2) inhibitors mepacrine or methyl 
      arachidonyl fluorophosphonate or the P-450 epoxygenase inhibitors 17-octadecynoic 
      acid or propargyloxyphenyl hexanoic acid. Similarly, combined pretreatment with 
      ibuprofen and dicyclohexylurea to block EET metabolism had no effect on the 
      permeability response to TG. We conclude that EETs have a heterogeneous impact on 
      EC permeability. Despite a requirement for Ca(2+) entry with both TG and 
      14,15-EET, our data suggest that distinct signaling pathways or heterogeneity in 
      EC responsiveness is responsible for the observed EC injury evoked by EETs and 
      store depletion in the isolated rat lung.
FAU - Alvarez, Diego F
AU  - Alvarez DF
AD  - Department of Physiology, University of Southern Alabama, Mobile, AL 36688, USA.
FAU - Gjerde, Eli-Anne B
AU  - Gjerde EA
FAU - Townsley, Mary I
AU  - Townsley MI
LA  - eng
GR  - HL-61955/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20031024
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Vasodilator Agents)
RN  - 5DOQ38R4UW (11,12-epoxy-5,8,14-eicosatrienoic acid)
RN  - 81246-84-6 (5,6-epoxy-8,11,14-eicosatrienoic acid)
RN  - 81246-85-7 (8,9-epoxyeicosatrienoic acid)
RN  - 81276-03-1 (14,15-epoxy-5,8,11-eicosatrienoic acid)
RN  - FC398RK06S (8,11,14-Eicosatrienoic Acid)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 8,11,14-Eicosatrienoic Acid/*analogs & derivatives/*pharmacology
MH  - Animals
MH  - Calcium/metabolism
MH  - Capillary Permeability/drug effects
MH  - Endothelium, Vascular/drug effects/metabolism
MH  - Lung/*blood supply/*drug effects
MH  - Male
MH  - Pulmonary Circulation/drug effects
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Vasodilator Agents/*pharmacology
EDAT- 2003/10/28 05:00
MHDA- 2004/03/05 05:00
CRDT- 2003/10/28 05:00
PHST- 2003/10/28 05:00 [pubmed]
PHST- 2004/03/05 05:00 [medline]
PHST- 2003/10/28 05:00 [entrez]
AID - 00150.2003 [pii]
AID - 10.1152/ajplung.00150.2003 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2004 Feb;286(2):L445-51. doi: 
      10.1152/ajplung.00150.2003. Epub 2003 Oct 24.