Inducible Endothelium-derived Hyperpolarizing Factor
| Autor: | William B. Campbell, Kathryn M. Gauthier |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Endothelium-derived hyperpolarizing factor Endothelium Bradykinin Vasodilation Biology Article Biological Factors chemistry.chemical_compound Internal medicine medicine Animals Arachidonate 15-Lipoxygenase Humans Pharmacology Arachidonic Acid Natriuretic Peptide C-Type Membrane hyperpolarization Potassium channel Up-Regulation Cell biology medicine.anatomical_structure Endocrinology chemistry cardiovascular system Endothelium Vascular Signal transduction Cardiology and Cardiovascular Medicine Acetylcholine Signal Transduction circulatory and respiratory physiology medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology. 61:176-187 |
| ISSN: | 0160-2446 |
| DOI: | 10.1097/fjc.0b013e31828165db |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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