File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Endothelium-derived hyperpolarizing factor

TitleEndothelium-derived hyperpolarizing factor
Authors
Issue Date1996
PublisherBlackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CEP
Citation
Clinical and Experimental Pharmacology & Physiology, 1996, v. 23 n. 12, p. 1082-1090 How to Cite?
Abstract1. Not all endothelium-dependent relaxations can be fully explained by the release of either nitric oxide (NO) and/or prostacyclin. Another unidentified substance(s) that hyperpolarizes the underlying vascular smooth muscle cells (endothelium-derived hyperpolarizing factor; EDHF) contributes to endothelium-dependent relaxations. 2. In blood vessels from various species these hyperpolarizations are resistant to inhibitors of NO synthase (NOS) and cyclo-oxygenase. In canine, porcine and human blood vessels the hyperpolarization cannot be mimicked by nitrovasodilators or exogeneous NO. However, in other species (rat, guinea-pig, rabbit) endothelium-dependent hyperpolarizations resistant to inhibitors of NOS and cyclo-oxygenase and hyperpolarizations to endothelium-derived or exogeneous NO can be observed in the same vascular smooth muscle cells. 3. In blood vessels where NO causes hyperpolarization, the response is blocked by glibenclamide, suggesting the involvement of ATP-dependent potassium channels. Hyperpolarizations caused by EDHF are insensitive to glibenclamide but, depending on the tissue, are inhibited by relatively small concentrations of tetraethylammonium (TEA) or by apamin or the combination of charybdotoxin plus apamin, indicating that calcium-dependent potassium channels are likely to be involved. 4. Metabolites of arachidonic acid, through the cytochrome P450 mono-oxygenase pathway (epoxyeicosatrienoic acids), are produced by the endothelial cells, increase the open-state probability of calcium-activated potassium channels sensitive to TEA or charybdotoxin, and induce the hyperpolarization of arterial smooth muscle cells, indicating that epoxyeicosatrienoic acids could be EDHF. However, in blood vessels from various species, cytochrome P450 inhibitors do not affect endothelium-dependent hyperpolarizations, indicating that EDHF is not yet identified with certainty. 5. Endothelium-derived hyperpolarizing factor released from cultured endothelial cells reduces the intracellular calcium concentration in vascular smooth muscle cells and the EDHF component of the relaxation is proportionally more important in smaller than larger arteries. In aging animals and in various models of diseases, endothelium-dependent hyperpolarizations are diminished. 6. The identification of EDHF and/or the discovery of specific inhibitors of its synthesis and its action may allow a better understanding of its physiological and pathophysiological role(s).
Persistent Identifierhttp://hdl.handle.net/10722/163621
ISSN
2012 Impact Factor: 2.16
2015 SCImago Journal Rankings: 0.944
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFélétou, M-
dc.contributor.authorVanhoutte, PMGR-
dc.date.accessioned2012-09-12T03:18:10Z-
dc.date.available2012-09-12T03:18:10Z-
dc.date.issued1996-
dc.identifier.citationClinical and Experimental Pharmacology & Physiology, 1996, v. 23 n. 12, p. 1082-1090-
dc.identifier.issn0305-1870-
dc.identifier.urihttp://hdl.handle.net/10722/163621-
dc.description.abstract1. Not all endothelium-dependent relaxations can be fully explained by the release of either nitric oxide (NO) and/or prostacyclin. Another unidentified substance(s) that hyperpolarizes the underlying vascular smooth muscle cells (endothelium-derived hyperpolarizing factor; EDHF) contributes to endothelium-dependent relaxations. 2. In blood vessels from various species these hyperpolarizations are resistant to inhibitors of NO synthase (NOS) and cyclo-oxygenase. In canine, porcine and human blood vessels the hyperpolarization cannot be mimicked by nitrovasodilators or exogeneous NO. However, in other species (rat, guinea-pig, rabbit) endothelium-dependent hyperpolarizations resistant to inhibitors of NOS and cyclo-oxygenase and hyperpolarizations to endothelium-derived or exogeneous NO can be observed in the same vascular smooth muscle cells. 3. In blood vessels where NO causes hyperpolarization, the response is blocked by glibenclamide, suggesting the involvement of ATP-dependent potassium channels. Hyperpolarizations caused by EDHF are insensitive to glibenclamide but, depending on the tissue, are inhibited by relatively small concentrations of tetraethylammonium (TEA) or by apamin or the combination of charybdotoxin plus apamin, indicating that calcium-dependent potassium channels are likely to be involved. 4. Metabolites of arachidonic acid, through the cytochrome P450 mono-oxygenase pathway (epoxyeicosatrienoic acids), are produced by the endothelial cells, increase the open-state probability of calcium-activated potassium channels sensitive to TEA or charybdotoxin, and induce the hyperpolarization of arterial smooth muscle cells, indicating that epoxyeicosatrienoic acids could be EDHF. However, in blood vessels from various species, cytochrome P450 inhibitors do not affect endothelium-dependent hyperpolarizations, indicating that EDHF is not yet identified with certainty. 5. Endothelium-derived hyperpolarizing factor released from cultured endothelial cells reduces the intracellular calcium concentration in vascular smooth muscle cells and the EDHF component of the relaxation is proportionally more important in smaller than larger arteries. In aging animals and in various models of diseases, endothelium-dependent hyperpolarizations are diminished. 6. The identification of EDHF and/or the discovery of specific inhibitors of its synthesis and its action may allow a better understanding of its physiological and pathophysiological role(s).-
dc.languageeng-
dc.publisherBlackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CEP-
dc.relation.ispartofClinical and Experimental Pharmacology & Physiology-
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.subject.meshAnimals-
dc.subject.meshBiological Factors - physiology-
dc.subject.meshEndothelium, Vascular - chemistry - physiology-
dc.subject.meshHumans-
dc.subject.meshMuscle, Smooth, Vascular - chemistry - physiology-
dc.titleEndothelium-derived hyperpolarizing factoren_US
dc.typeArticleen_US
dc.identifier.emailVanhoutte, PMGR: vanhoutt@hku.hk-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1440-1681.1996.tb01174.x-
dc.identifier.pmid8977164-
dc.identifier.scopuseid_2-s2.0-0030451525-
dc.identifier.volume23-
dc.identifier.issue12-
dc.identifier.spage1082-
dc.identifier.epage1090-
dc.identifier.isiWOS:A1996VZ70100014-
dc.publisher.placeAustralia-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats