Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11586
Full metadata record
DC FieldValueLanguage
dc.contributor.authorHerath, Chandana Ben
dc.contributor.authorMak, Kaien
dc.contributor.authorBurrell, Louise Men
dc.contributor.authorAngus, Peter Wen
dc.date.accessioned2015-05-16T01:12:05Z
dc.date.available2015-05-16T01:12:05Z
dc.date.issued2012-10-18en
dc.identifier.citationAmerican Journal of Physiology. Gastrointestinal and Liver Physiology 2012; 304(1): G99-108en
dc.identifier.govdoc23086915en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/11586en
dc.description.abstractRecent studies have shown that, in cirrhosis, portal angiotensin-(1-7) [Ang-(1-7)] levels are increased and hepatic expression of angiotensin converting enzyme 2 (ACE2) and the Mas receptor are upregulated, but the effects of Ang-(1-7) on hepatic hemodynamics in cirrhosis have not been studied. This study investigated the effects of Ang-(1-7) on vasoconstrictor-induced perfusion pressure increases in cirrhotic rat livers. Ang II or the alpha 1 agonist methoxamine (MTX) were injected in the presence or absence of Ang-(1-7), and the perfusion pressure response was recorded. Denudation of vascular endothelial cells with sodium deoxycholate was used to investigate the contribution of endothelium to the effects of Ang-(1-7). Ang-(1-7) alone had no effect on perfusion pressure. However, it reduced the maximal vasoconstriction response and area under the pressure response curve to Ang II and MTX by >50% (P < 0.05). This effect of Ang-(1-7) was not blocked by Mas receptor inhibition with A779 or by Ang II type 1 and type 2 receptor and bradykinin B(2) receptor blockade and was not reproduced by the Mas receptor agonist AVE0991. D-Pro(7)-Ang-(1-7), a novel Ang-(1-7) receptor antagonist, completely abolished the vasodilatory effects of Ang-(1-7), as did inhibition of endothelial nitric oxide synthase (eNOS) with N(G)-nitro-L-arginine methyl-ester, guanylate cyclase blockade with ODQ and endothelium denudation. The functional inhibition by D-Pro(7)-Ang-(1-7) was accompanied by significant (P < 0.05) inhibition of eNOS phosphorylation. This study shows that Ang-(1-7) significantly inhibits intrahepatic vasoconstriction in response to key mediators of increased vascular and sinusoidal tone in cirrhosis via a receptor population present on the vascular endothelium that is sensitive to D-Pro(7)-Ang-(1-7) and causes activation of eNOS and guanylate cyclase-dependent NO signaling pathways.en
dc.language.isoenen
dc.subject.otherAngiotensin I.pharmacologyen
dc.subject.otherAngiotensin II.pharmacologyen
dc.subject.otherAnimalsen
dc.subject.otherBlood Pressure.drug effectsen
dc.subject.otherBlotting, Westernen
dc.subject.otherEndothelium, Vascular.metabolism.physiologyen
dc.subject.otherIn Situ Hybridizationen
dc.subject.otherLiver.metabolism.pathologyen
dc.subject.otherLiver Circulation.drug effectsen
dc.subject.otherLiver Cirrhosis.pathology.physiopathologyen
dc.subject.otherMaleen
dc.subject.otherMethoxamine.antagonists & inhibitors.pharmacologyen
dc.subject.otherNitric Oxide.physiologyen
dc.subject.otherNitric Oxide Synthase Type III.metabolismen
dc.subject.otherPeptide Fragments.pharmacologyen
dc.subject.otherPhosphorylationen
dc.subject.otherRatsen
dc.subject.otherRats, Sprague-Dawleyen
dc.subject.otherReceptor, Angiotensin, Type 1.drug effectsen
dc.subject.otherReceptor, Angiotensin, Type 2.drug effectsen
dc.subject.otherReceptor, Bradykinin B2.drug effectsen
dc.subject.otherVasoconstrictor Agents.antagonists & inhibitors.pharmacologyen
dc.titleAngiotensin-(1-7) reduces the perfusion pressure response to angiotensin II and methoxamine via an endothelial nitric oxide-mediated pathway in cirrhotic rat liver.en
dc.typeJournal Articleen
dc.identifier.journaltitleAmerican journal of physiology. Gastrointestinal and liver physiologyen
dc.identifier.affiliationDepartment of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Victoria, Australiaen
dc.identifier.doi10.1152/ajpgi.00163.2012en
dc.description.pagesG99-108en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/23086915en
dc.type.austinJournal Articleen
item.grantfulltextnone-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.cerifentitytypePublications-
crisitem.author.deptCardiology-
crisitem.author.deptGeneral Medicine-
crisitem.author.deptMedicine (University of Melbourne)-
crisitem.author.deptVictorian Liver Transplant Unit-
crisitem.author.deptGastroenterology and Hepatology-
Appears in Collections:Journal articles
Show simple item record

Page view(s)

16
checked on Feb 6, 2023

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.