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Renal vascular smooth muscle expression of the NO receptor, soluble GC (sGC), modulates the vasodilator response needed to control renal vascular tone and blood flow. Here, we tested if angiotensin II (Ang II) affects sGC expression via an AT<jats:sub>1<\/jats:sub> receptor\u2010forkhead box subclass O (FoxO) transcription factor dependent mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Using a murine two\u2010kidney\u2010one\u2010clip (2K1C) renovascular hypertension model, we measured renal artery vasodilatory function and sGC expression. Additionally, we conducted cell culture studies using rat renal pre\u2010glomerular smooth muscle cells (RPGSMCs) to test the in vitro mechanistic effects of Ang II treatment on sGC expression and downstream function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Contralateral, unclipped renal arteries in 2K1C mice showed increased NO\u2010dependent vasorelaxation compared to sham control mice. Immunofluorescence studies revealed increased sGC protein expression in 2K1C contralateral renal arteries over sham controls. RPGSMCs treated with Ang II caused a significant up\u2010regulation of sGC mRNA and protein expression as well as downstream sGC\u2010dependent signalling. Ang II signalling effects on sGC expression occurred through an AT<jats:sub>1<\/jats:sub> receptor and FoxO transcription factor\u2010dependent mechanism at both the mRNA and protein expression levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Renal artery smooth muscle, in vivo and in vitro, up\u2010regulates expression of sGC following RAAS activity. In both cases, up\u2010regulation of sGC leads to increased downstream cGMP signalling, suggesting a previously unrecognized protective mechanism to improve renal blood flow in the uninjured contralateral renal artery.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v179.11\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v179.11\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15522","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T05:49:31Z","timestamp":1620539371000},"page":"2490-2504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Angiotensin II augments renal vascular smooth muscle soluble GC expression via an AT<sub>1<\/sub> receptor\u2013forkhead box subclass O transcription factor signalling axis"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3463-8390","authenticated-orcid":false,"given":"Joseph C.","family":"Galley","sequence":"first","affiliation":[{"name":"Heart, Lung, Blood and 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