Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11586
Title: Angiotensin-(1-7) reduces the perfusion pressure response to angiotensin II and methoxamine via an endothelial nitric oxide-mediated pathway in cirrhotic rat liver.
Austin Authors: Herath, Chandana B;Mak, Kai;Burrell, Louise M ;Angus, Peter W 
Affiliation: Medicine (University of Melbourne)
Issue Date: 18-Oct-2012
Publication information: American Journal of Physiology. Gastrointestinal and Liver Physiology 2012; 304(1): G99-108
Abstract: Recent 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.
URI: https://ahro.austin.org.au/austinjspui/handle/1/11586
DOI: 10.1152/ajpgi.00163.2012
ORCID: 
Journal: American Journal of Physiology. Gastrointestinal and Liver Physiology
URL: https://pubmed.ncbi.nlm.nih.gov/23086915
Type: Journal Article
Subjects: Angiotensin I.pharmacology
Angiotensin II.pharmacology
Animals
Blood Pressure.drug effects
Blotting, Western
Endothelium, Vascular.metabolism.physiology
In Situ Hybridization
Liver.metabolism.pathology
Liver Circulation.drug effects
Liver Cirrhosis.pathology.physiopathology
Male
Methoxamine.antagonists & inhibitors.pharmacology
Nitric Oxide.physiology
Nitric Oxide Synthase Type III.metabolism
Peptide Fragments.pharmacology
Phosphorylation
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1.drug effects
Receptor, Angiotensin, Type 2.drug effects
Receptor, Bradykinin B2.drug effects
Vasoconstrictor Agents.antagonists & inhibitors.pharmacology
Appears in Collections:Journal articles

Show full item record

Page view(s)

44
checked on Mar 28, 2024

Google ScholarTM

Check


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