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https://hdl.handle.net/11055/35
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DC Field | Value | Language |
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dc.contributor.author | Angus, JA | - |
dc.contributor.author | Soeding, PF | - |
dc.contributor.author | Hughes, RJA | - |
dc.contributor.author | Wright, CE | - |
dc.date | 2017-03-11 | - |
dc.date.accessioned | 2017-11-09T01:29:30Z | - |
dc.date.available | 2017-11-09T01:29:30Z | - |
dc.date.issued | 2017-06 | - |
dc.identifier.citation | Angus JA, Soeding PF, Hughes RJA, Wright CE. Functional estimation of endothelin-1 receptor antagonism by bosentan, macitentan and ambrisentan in human pulmonary and radial arteries in vitro. Eur J Pharmacol. 2017; 804:111-116. | en_US |
dc.identifier.issn | 0014-2999 | en_US |
dc.identifier.uri | http://hdl.handle.net/11055/35 | - |
dc.description.abstract | Endothelin receptor antagonists are approved for pulmonary arterial hypertension. Development of selective ETA-receptor antagonists over mixed or dual receptor antagonists has depended on a range of receptor binding assays, second messenger assays and functional blood vessel assays. This study compared the 3 clinically-approved endothelin receptor antagonists in assays of human isolated pulmonary and radial arteries in vitro. METHODS: Human isolated pulmonary (i.d. 5.5mm) and human radial (i.d. 3.23mm) artery ring segments were mounted in organ baths for isometric force measurement. Single concentration-contraction curves to endothelin-1 were constructed in the absence or presence of bosentan (1-10µM), macitentan (0.03-0.3µM) or ambrisentan (0.1-1µM). RESULTS: All 3 endothelin antagonists caused competitive rightward shifts in the endothelin-1 concentration-response curves in both arteries. The Clark plot and analysis gave the following pKB values: bosentan, pulmonary artery 6.28±0.13 and radial artery 6.04±0.10; macitentan, pulmonary artery 8.02±0.13 and radial artery 7.49±0.08; and ambrisentan, pulmonary artery 7.38±0.13 and radial artery 6.96±0.10. CONCLUSIONS: Noting the maximum plasma levels attained from recommended oral doses of each antagonist in volunteers, the pKB findings here show that there would be significant antagonism of endothelin-1 contraction in the pulmonary and radial arteries at therapeutic plasma levels. This functional assay confirms in human tissue that much higher plasma concentrations of endothelin-1 receptor antagonists are required to be effective than those predicted from binding or other biochemical assays. | en_US |
dc.subject | Bosentan | en_US |
dc.subject | Endothelin-1 | en_US |
dc.subject | macitentan | en_US |
dc.subject | ambrisentan | en_US |
dc.subject | Human pulmonary artery | en_US |
dc.subject | Human radial artery | en_US |
dc.title | Functional estimation of endothelin-1 receptor antagonism by bosentan, macitentan and ambrisentan in human pulmonary and radial arteries in vitro | en_US |
dc.type | Journal Article | en_US |
dc.type.content | Text | en_US |
dc.identifier.journaltitle | European journal of pharmacology | en_US |
dc.identifier.doi | 10.1016/j.ejphar.2017.03.014 | en_US |
dc.description.affiliates | Australian and New Zealand College of Anaesthetists | en_US |
dc.description.pubmeduri | https://www.ncbi.nlm.nih.gov/pubmed/28300593 | en_US |
dc.ispartof.anzcaresearchfoundation | Yes | - |
item.grantfulltext | none | - |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
item.openairetype | Journal Article | - |
Appears in Collections: | Scholarly and Clinical |
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