Linked Life Data

18533738

Source:http://linkedlifedata.com/resource/pubmed/id/18533738

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-6-6
pubmed:abstractText
The last decade has seen significant advances in the understanding and treatment of pulmonary arterial hypertension (PAH). Three main pathways, involving endothelin, nitric oxide, and prostacyclin, have been identified in its pathogenesis and these have all led to the development of therapies in current use. While the nitric oxide and prostacyclin pathways require augmentation, the endothelin system is overactive in PAH, with increased endothelin synthesis and receptor expression and, therefore, requires blockade. There are two known endothelin receptors. The type A receptor, expressed in pulmonary artery media, mediates vasoconstriction and remodeling, whereas the function of the type B receptor is more complex. Like the type A receptor, the type B receptor mediates vasoconstriction and remodeling effects when expressed on smooth muscle cells and (myo)fibroblasts, yet functions to clear endothelin from the circulation and induce release of endogenous nitric oxide and prostacyclin, when activated in the pulmonary artery endothelium. Consequently, it is not clear from in vitro data whether the optimal strategy is to block only the type A receptor or both receptors. Phase III clinical studies show clear short-term physiologic benefit with both dual and selective endothelin blockade in PAH. Longer-term experience with bosentan, a dual receptor antagonist, has shown improved outcomes compared with historic control data and comparable survival to intravenous prostacyclin therapy. The newer selective blockers, sitaxsentan and ambrisentan, appear to have similar short-term efficacy, but long-term data are as yet either lacking or unpublished. They may be less hepatotoxic than bosentan, although long-term follow-up of patients receiving bosentan has shown this is not a significant problem. On the basis of available evidence, the endothelin receptor antagonists have become first-line therapy for patients with PAH, except in the most severely affected who still require treatment with intravenous prostacyclin. Although their use as part of combination therapy with other agents is widespread, the evidence for this is not as robust, but appropriate investigation is underway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1175-3277
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
171-85
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Endothelin receptor antagonists for pulmonary arterial hypertension: rationale and place in therapy.
pubmed:affiliation
Department of Cardiac Sciences, National Pulmonary Hypertension Service, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.
pubmed:publicationType
Journal Article, Review