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We tested the contribution of the renin\u2013angiotensin system to the effects of acute intermittent hypoxia (AIH) in anaesthetized and ventilated rats. There was a 33.7\u00a0\u00b1\u00a02.9% increase in sympathetic nerve activity (SNA), while sympathetic chemoreflex sensitivity and central sympathetic\u2013respiratory coupling increased by one\u2010fold following AIH. The sympathetic effects of AIH were prevented by blocking angiotensin type 1 receptors with systemic losartan. Intermittent systemic injections of Ang\u00a0II (Int.Ang\u00a0II) elicited similar sympathetic responses to AIH. To identify the neural pathways responsible for the effects of AIH and Int.Ang\u00a0II, we performed bilateral carotid body denervation, which reduced the increase in SNA by 56% and 45%, respectively. Conversely, pharmacological inhibition of the subfornical organ (SFO), an established target of circulating Ang\u00a0II, reduced the increase in SNA following AIH and Int.Ang\u00a0II by 65% and 59%, respectively, although it did not prevent the sensitization of the sympathetic peripheral chemoreflex, nor the increase in central sympathetic\u2013respiratory coupling. Combined carotid body denervation and inhibition of the SFO eliminated the enhancement of SNA following AIH and Int.Ang\u00a0II. Repeated systemic injections of phenylephrine caused an elevation in SNA similar to AIH, and this effect was prevented by a renin inhibitor, aliskiren. Our findings show that the sympathetic effects of AIH are the result of RAS\u2010mediated activations of the carotid bodies and the SFO.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp275804","type":"journal-article","created":{"date-parts":[[2018,4,12]],"date-time":"2018-04-12T09:46:43Z","timestamp":1523526403000},"page":"3217-3232","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Sympathoexcitation following intermittent hypoxia in rat is mediated by circulating angiotensin II acting at the carotid body and subfornical organ"],"prefix":"10.1113","volume":"596","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0268-6029","authenticated-orcid":false,"given":"Seung Jae","family":"Kim","sequence":"first","affiliation":[{"name":"Sydney Medical School University of Sydney  Sydney NSW Australia"},{"name":"Heart Research Institute  7 Eliza Street, Newtown Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina Y.","family":"Fong","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Melbourne  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3500-467X","authenticated-orcid":false,"given":"Paul M.","family":"Pilowsky","sequence":"additional","affiliation":[{"name":"Sydney Medical School University of Sydney  Sydney NSW Australia"},{"name":"Heart Research Institute  7 Eliza Street, Newtown Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1244-3637","authenticated-orcid":false,"given":"Stephen B. 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