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Ang II or the alpha 1 agonist methoxamine (MTX) were injected in the presence or absence of Ang-(1\u20137), 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\u20137). Ang-(1\u20137) 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 &gt;50% ( P &lt; 0.05). This effect of Ang-(1\u20137) was not blocked by Mas receptor inhibition with A779 or by Ang II type 1 and type 2 receptor and bradykinin B<jats:sub>2<\/jats:sub>receptor blockade and was not reproduced by the Mas receptor agonist AVE0991. D-Pro<jats:sup>7<\/jats:sup>-Ang-(1\u20137), a novel Ang-(1\u20137) receptor antagonist, completely abolished the vasodilatory effects of Ang-(1\u20137), as did inhibition of endothelial nitric oxide synthase (eNOS) with N<jats:sup>G<\/jats:sup>-nitro-l -arginine methyl-ester, guanylate cyclase blockade with ODQ and endothelium denudation. The functional inhibition by D-Pro<jats:sup>7<\/jats:sup>-Ang-(1\u20137) was accompanied by significant ( P &lt; 0.05) inhibition of eNOS phosphorylation. This study shows that Ang-(1\u20137) 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<jats:sup>7<\/jats:sup>-Ang-(1\u20137) and causes activation of eNOS and guanylate cyclase-dependent NO signaling pathways.<\/jats:p>","DOI":"10.1152\/ajpgi.00163.2012","type":"journal-article","created":{"date-parts":[[2012,10,20]],"date-time":"2012-10-20T01:21:19Z","timestamp":1350696079000},"page":"G99-G108","source":"Crossref","is-referenced-by-count":23,"title":["Angiotensin-(1\u20137) reduces the perfusion pressure response to angiotensin II and methoxamine via an endothelial nitric oxide-mediated pathway in cirrhotic rat liver"],"prefix":"10.1152","volume":"304","author":[{"given":"Chandana B.","family":"Herath","sequence":"first","affiliation":[{"name":"Department of Medicine, The University of Melbourne, Austin Health, 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