The role of endothelin in mediating ischemia/hypoxia-induced atrial natriuretic peptide release

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dc.contributor.authorZhang, Y.
dc.contributor.authorOliver, J.
dc.contributor.authorHorowitz, J.
dc.date.issued2004
dc.description© 2004 Lippincott Williams & Wilkins, Inc.
dc.description.abstractThe aim of the present study was to investigate the putative role of endothelin (ET) in mediating ischemia/hypoxia-induced ANP release utilizing exogenous ET-1 or ET receptor antagonists (BQ-123 or Bosentan). Isolated rat hearts with non-distended atria were perfused using a Langendorff apparatus and heart rate maintained constant via atrial pacing. Global ischemia was induced either by direct reduction in perfusion or by infusion of exogenous ET-1 (5 x 10(-10) M) for 30 minutes. Perfusion with the ET receptor antagonists, BQ-123 (10(-6) M) or Bosentan (10(-5) M) was initiated 10 minutes before onset of ischemia. Moderate or severe ischemia was induced by reduction (52-61% and 70-82%, respectively) in perfusate flow. Thirty minutes of ischemia/hypoxia (5% O2) was followed by 30 minutes of reperfusion/re-oxygenation. Both moderate and severe ischemia increased ANP release. BQ-123 and Bosentan did not affect basal or ischemia-induced ANP release. Exogenous ET-1 perfusion induced a late increase in ANP release (P < 0.01) that did not exceed the increase in ANP release associated with equivalent direct flow reduction. Hypoxia induced an 8-fold increase in ANP release rate. The ANP release rate returned toward basal levels after re-oxygenation. Bosentan, but not BQ-123, significantly attenuated (P < 0.01) hypoxia-induced ANP release. In conclusion, in this system, ANP release is stimulated by moderate (or severe) ischemia and severe hypoxia independent of change in atrial distension; endogenous ET does not mediate basal and ischemia-induced ANP release; and hypoxia-induced ANP release is partially modulated via interaction with endogenous ET.
dc.description.statementofresponsibilityYi Zhang, John R. Oliver, and John D. Horowitz
dc.identifier.citationJournal of Cardiovascular Pharmacology, 2004; 43(2):227-233
dc.identifier.doi10.1097/00005344-200402000-00010
dc.identifier.issn0160-2446
dc.identifier.issn1533-4023
dc.identifier.orcidHorowitz, J. [0000-0001-6883-0703]
dc.identifier.urihttp://hdl.handle.net/2440/9917
dc.language.isoen
dc.publisherLippincott Williams & Wilkins
dc.source.urihttp://journals.lww.com/cardiovascularpharm/pages/articleviewer.aspx?year=2004&issue=02000&article=00010&type=abstract
dc.subjectANP
dc.subjectendothelin
dc.subjectendothelin receptor antagonists
dc.subjecthypoxia
dc.subjectischemia
dc.subjectisolated rat heart
dc.titleThe role of endothelin in mediating ischemia/hypoxia-induced atrial natriuretic peptide release
dc.typeJournal article
pubs.publication-statusPublished

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