Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11802
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dc.contributor.authorGrace, Josephine A-
dc.contributor.authorKlein, Sabine-
dc.contributor.authorHerath, Chandana B-
dc.contributor.authorGranzow, Michaela-
dc.contributor.authorSchierwagen, Robert-
dc.contributor.authorMasing, Noemi-
dc.contributor.authorWalther, Thomas-
dc.contributor.authorSauerbruch, Tilman-
dc.contributor.authorBurrell, Louise M-
dc.contributor.authorAngus, Peter W-
dc.contributor.authorTrebicka, Jonel-
dc.date.accessioned2015-05-16T01:25:49Z
dc.date.available2015-05-16T01:25:49Z
dc.date.issued2013-06-22-
dc.identifier.citationGastroenterology 2013; 145(4): 874-884.e5en_US
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/11802en
dc.description.abstractSplanchnic vascular hypocontractility with subsequent increased portal venous inflow leads to portal hypertension. Although the renin-angiotensin system contributes to fibrogenesis and increased hepatic resistance in patients with cirrhosis, little is known about its effects in the splanchnic vasculature, particularly those of the alternate system in which angiotensin (Ang) II is cleaved by the Ang-converting enzyme-2 (ACE2) to Ang-(1-7), which activates the G-protein-coupled Mas receptor (MasR). We investigated whether this system contributes to splanchnic vasodilatation and portal hypertension in cirrhosis.We measured levels of renin-angiotensin system messenger RNA and proteins in splanchnic vessels from patients and rats with cirrhosis. Production of Ang-(1-7) and splanchnic vascular reactivity to Ang-(1-7) was measured in perfused mesenteric vascular beds from rats after bile-duct ligation. Ang-(1-7) and MasR were blocked in rats with cirrhosis to examine splanchnic vascular hemodynamics and portal pressure response.Levels of ACE2 and MasR were increased in splanchnic vessels from cirrhotic patients and rats compared with healthy controls. We also observed an ACE2-dependent increase in Ang-(1-7) production. Ang-(1-7) mediated splanchnic vascular hypocontractility in ex vivo splanchnic vessels from rats with cirrhosis (but not control rats) via MasR stimulation. Identical effects were observed in the splanchnic circulation in vivo. MasR blockade reduced portal pressure, indicating that activation of this receptor in splanchnic vasculature promotes portal inflow to contribute to development of portal hypertension. In addition, the splanchnic effects of MasR required nitric oxide. Interestingly, Ang-(1-7) also decreased hepatic resistance.In the splanchnic vessels of patients and rats with cirrhosis, increased levels of ACE2 appear to increase production of Ang-(1-7), which leads to activation of MasR and splanchnic vasodilatation in rats. This mechanism could cause vascular hypocontractility in patients with cirrhosis, and might be a therapeutic target for portal hypertension.en_US
dc.language.isoenen
dc.subject.otherACEen
dc.subject.otherAT1Ren
dc.subject.otherAT2Ren
dc.subject.otherAngen
dc.subject.otherBDLen
dc.subject.otherCCl(4)en
dc.subject.otherHVRen
dc.subject.otherHemodynamicsen
dc.subject.otherMas receptoren
dc.subject.otherMasRen
dc.subject.otherNOSen
dc.subject.otherPPen
dc.subject.otherPortal Hypertensionen
dc.subject.otherRASen
dc.subject.otherRat Modelen
dc.subject.otherSpVRen
dc.subject.otherVASPen
dc.subject.otherangiotensinen
dc.subject.otherangiotensin II type 1 receptoren
dc.subject.otherangiotensin II type 2 receptoren
dc.subject.otherangiotensin-converting enzymeen
dc.subject.otherbile duct ligationen
dc.subject.othercarbon tetrachlorideen
dc.subject.othereNOSen
dc.subject.otherendothelial nitric oxide synthaseen
dc.subject.otherhepatic vascular resistanceen
dc.subject.otheriNOSen
dc.subject.otherinducible nitric oxide synthaseen
dc.subject.othernitric oxide synthaseen
dc.subject.otherportal pressureen
dc.subject.otherrenin−angiotensin systemen
dc.subject.othersplanchnic vascular resistanceen
dc.subject.othervasodilator-stimulated phosphoproteinen
dc.subject.otherAngiotensin I.pharmacologyen
dc.subject.otherAnimalsen
dc.subject.otherHumansen
dc.subject.otherLiver Cirrhosis, Experimental.physiopathologyen
dc.subject.otherMesenteric Arteries.physiopathologyen
dc.subject.otherNitric Oxide.physiologyen
dc.subject.otherPeptide Fragments.pharmacologyen
dc.subject.otherPeptidyl-Dipeptidase A.physiologyen
dc.subject.otherProto-Oncogene Proteins.metabolismen
dc.subject.otherRatsen
dc.subject.otherReceptors, G-Protein-Coupled.drug effects.metabolism.physiologyen
dc.subject.otherRenin-Angiotensin System.drug effectsen
dc.subject.otherVascular Resistanceen
dc.subject.otherVasodilation.physiologyen
dc.titleActivation of the MAS receptor by angiotensin-(1-7) in the renin-angiotensin system mediates mesenteric vasodilatation in cirrhosis.en_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleGastroenterologyen_US
dc.identifier.affiliationGeneral Medicineen_US
dc.identifier.affiliationAustin Healthen_US
dc.identifier.doi10.1053/j.gastro.2013.06.036en_US
dc.description.pages874-884.e5en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/23796456en
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.deptGastroenterology and Hepatology-
crisitem.author.deptMedicine (University of Melbourne)-
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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