PMID- 23249676
OWN - NLM
STAT- MEDLINE
DCOM- 20130903
LR  - 20211021
IS  - 1533-4023 (Electronic)
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 61
IP  - 3
DP  - 2013 Mar
TI  - Inducible endothelium-derived hyperpolarizing factor: role of the 
      15-lipoxygenase-EDHF pathway.
PG  - 176-87
LID - 10.1097/FJC.0b013e31828165db [doi]
AB  - Endothelium-derived hyperpolarizing factors (EDHFs) regulate vascular tone by 
      contributing to the vasorelaxations to shear stress and endothelial agonists such 
      as bradykinin and acetylcholine. 15(S)-Hydroxy-11,12-epoxyeicosatrienoic acid 
      (15-H-11,12-EETA) and 11(R),12(S),15(S)-trihydroxyeicosatrienoic acid 
      (11,12,15-THETA) are endothelial metabolites of the 15-lipoxygenase (15-LO) 
      pathway of arachidonic acid metabolism and are EDHFs. 11,12,15-THETA activates 
      small conductance, calcium-activated potassium channels on smooth muscle cells 
      causing membrane hyperpolarization, and relaxation. Expression levels of 15-LO in 
      the endothelium regulate the activity of the 15-LO/15-H-11,12-EETA/11,12,15-THETA 
      pathway and its contribution to vascular tone. Regulation of its expression is by 
      transcriptional, translational, and epigenetic mechanisms. Hypoxia, 
      hypercholesterolemia, atherosclerosis, anemia, estrogen, interleukins, and 
      possibly other hormones increase 15-LO expression. An increase in 15-LO results 
      in increased synthesis of 15-H-11,12-EETA and 11,12,15-THETA, increased membrane 
      hyperpolarization, and enhanced contribution to relaxation by endothelial 
      agonists. Thus, the 15-LO pathway represents the first example of an inducible 
      EDHF. In addition to 15-LO metabolites, a number of chemicals have been 
      identified as EDHFs and their contributions to vascular tone vary with species 
      and vascular bed. The reason for multiple EDHFs has evaded explanation. However, 
      EDHF functioning as constitutive EDHFs or inducible EDHFs may explain the need 
      for chemically and biochemically distinct pathways for EDHF activity and the 
      variation in EDHFs between species and vascular beds. This new EDHF 
      classification provides a framework for understanding EDHF activity in 
      physiological and pathological conditions.
FAU - Campbell, William B
AU  - Campbell WB
AD  - Department of Pharmacology and Toxicology, Medical College of Wisconsin, 
      Milwaukee, WI 53226, USA. wbcamp@mcw.edu
FAU - Gauthier, Kathryn M
AU  - Gauthier KM
LA  - eng
GR  - R01 HL037981/HL/NHLBI NIH HHS/United States
GR  - R01 HL103673/HL/NHLBI NIH HHS/United States
GR  - HL-37981/HL/NHLBI NIH HHS/United States
GR  - HL-103673/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Biological Factors)
RN  - 0 (endothelium-dependent hyperpolarization factor)
RN  - 127869-51-6 (Natriuretic Peptide, C-Type)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - EC 1.13.11.33 (ALOX15 protein, human)
RN  - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase)
SB  - IM
MH  - Animals
MH  - Arachidonate 15-Lipoxygenase/biosynthesis/*metabolism
MH  - Arachidonic Acid/metabolism
MH  - Biological Factors/biosynthesis/*metabolism
MH  - Endothelium, Vascular/enzymology/*metabolism
MH  - Humans
MH  - Natriuretic Peptide, C-Type/metabolism
MH  - *Signal Transduction
MH  - *Up-Regulation
MH  - Vasodilation
PMC - PMC3594564
MID - NIHMS433260
EDAT- 2012/12/20 06:00
MHDA- 2013/09/04 06:00
PMCR- 2014/03/01
CRDT- 2012/12/20 06:00
PHST- 2012/12/20 06:00 [entrez]
PHST- 2012/12/20 06:00 [pubmed]
PHST- 2013/09/04 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - 10.1097/FJC.0b013e31828165db [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2013 Mar;61(3):176-87. doi: 10.1097/FJC.0b013e31828165db.