Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/10807
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dc.contributor.authorHerath, Chandana B-
dc.contributor.authorLubel, John S-
dc.contributor.authorJia, Zhiyuan-
dc.contributor.authorVelkoska, Elena-
dc.contributor.authorCasley, David J-
dc.contributor.authorBrown, Lindsay-
dc.contributor.authorTikellis, Christos-
dc.contributor.authorBurrell, Louise M-
dc.contributor.authorAngus, Peter W-
dc.date.accessioned2015-05-16T00:22:37Z
dc.date.available2015-05-16T00:22:37Z
dc.date.issued2009-04-23-
dc.identifier.citationAmerican Journal of Physiology. Gastrointestinal and Liver Physiology 2009; 297(1): G98-G106en_US
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/10807en
dc.description.abstractAngiotensin converting enzyme (ACE) 2 activity and angiotensin-(1-7) [Ang-(1-7)] levels are increased in experimental cirrhosis; however, the pathways of hepatic Ang-(1-7) production have not been studied. This study investigated the role of ACE2, ACE, and neutral endopeptidase (NEP) in the hepatic formation of Ang-(1-7) from angiotensin I (Ang I) and Ang II and their effects on portal resistance. Ang I or Ang II were administered to rat bile duct ligated (BDL) and control livers alone and in combination with the ACE inhibitor lisinopril, the ACE and NEP inhibitor omapatrilat, or the ACE2 inhibitor MLN4760 (n = 5 per group). BDL markedly upregulated ACE, ACE2, and NEP. Ang-(1-7) was produced from Ang II in healthy and in BDL livers and was increased following ACE inhibition and decreased by ACE2 inhibition. In contrast, Ang-(1-7) production from Ang I was minimal and not affected by ACE or NEP inhibition. Surprisingly, ACE2 inhibition in BDLs dramatically increased Ang-(1-7) production from Ang I, an effect abolished by ACE2/NEP inhibition. Ang II and Ang I induced greater portal pressure increases in BDL livers than controls. The effects of Ang I were closely correlated with Ang II production and were strongly attenuated by both ACE and ACE/NEP inhibition. These findings show that the major substrate for hepatic production of Ang-(1-7) is Ang II and this is catalyzed by ACE2. Ang I is largely converted to Ang II by ACE, and net conversion of Ang I to Ang-(1-7) is small. NEP has the ability to generate large amounts of Ang-(1-7) in the BDL liver from Ang I only when ACE2 activity is greatly decreased or inhibited.en_US
dc.language.isoenen
dc.subject.otherAngiotensin I.metabolismen
dc.subject.otherAngiotensin II.metabolismen
dc.subject.otherAngiotensin-Converting Enzyme Inhibitors.pharmacologyen
dc.subject.otherAngiotensins.administration & dosage.metabolismen
dc.subject.otherAnimalsen
dc.subject.otherCommon Bile Duct.surgeryen
dc.subject.otherGene Expression Regulation, Enzymologicen
dc.subject.otherImidazoles.pharmacologyen
dc.subject.otherLeucine.analogs & derivatives.pharmacologyen
dc.subject.otherLigationen
dc.subject.otherLisinopril.pharmacologyen
dc.subject.otherLiver.blood supply.drug effects.enzymology.pathologyen
dc.subject.otherLiver Cirrhosis, Experimental.drug therapy.enzymology.etiology.physiopathologyen
dc.subject.otherMaleen
dc.subject.otherNeprilysin.antagonists & inhibitors.metabolismen
dc.subject.otherPeptide Fragments.metabolismen
dc.subject.otherPeptidyl-Dipeptidase A.genetics.metabolismen
dc.subject.otherPortal Pressure.drug effectsen
dc.subject.otherPyridines.pharmacologyen
dc.subject.otherRatsen
dc.subject.otherRats, Sprague-Dawleyen
dc.subject.otherRenin-Angiotensin System.geneticsen
dc.subject.otherSeverity of Illness Indexen
dc.subject.otherThiazepines.pharmacologyen
dc.subject.otherTime Factorsen
dc.subject.otherVascular Resistanceen
dc.titlePortal pressure responses and angiotensin peptide production in rat liver are determined by relative activity of ACE and ACE2.en_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleAmerican Journal of Physiology. Gastrointestinal and Liver Physiologyen_US
dc.identifier.affiliationMedicine (University of Melbourne)en_US
dc.identifier.doi10.1152/ajpgi.00045.2009en_US
dc.description.pagesG98-G106en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/19389807en
dc.type.contentTexten_US
dc.type.austinJournal Articleen
local.name.researcherAngus, Peter W
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptCardiology-
crisitem.author.deptGeneral Medicine-
crisitem.author.deptMedicine (University of Melbourne)-
crisitem.author.deptVictorian Liver Transplant Unit-
crisitem.author.deptGastroenterology and Hepatology-
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