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We have previously shown that carotid sinus nerve denervation (CSD) reduces arterial blood pressure (ABP) in SHR. In the present study, we show that CSD ameliorates 2K1C hypertension and reveal the potential underlying mechanisms. Adult Wistar rats were instrumented to record ABP via telemetry, and then underwent CSD (<jats:italic>n<\/jats:italic>\u00a0=\u00a09) or sham CSD (<jats:italic>n<\/jats:italic>\u00a0=\u00a09) 5\u00a0weeks after renal artery clipping, in comparison with normal Wistar rats (<jats:italic>n<\/jats:italic>\u00a0=\u00a05). After 21\u00a0days, renal function was assessed, and tissue was collected to assess sympathetic postganglionic intracellular calcium transients ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) and immune cell infiltrates. Hypertensive 2K1C rats showed a profound elevation in ABP (Wistar: 98\u00a0\u00b1\u00a04\u00a0mmHg<jats:italic>vs<\/jats:italic>. 2K1C: 147\u00a0\u00b1\u00a08\u00a0mmHg;<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), coupled with impairments in renal function and baroreflex sensitivity, increased neuroinflammatory markers and enhanced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>I<\/jats:sub>in stellate neurons (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). CSD reduced ABP in 2K1C+CSD rats and prevented the further progressive increase in ABP seen in 2K1C+sham CSD rats, with a between\u2010group difference of 14\u00a0\u00b1\u00a02\u00a0mmHg by week 3 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), which was accompanied by improvements in both baroreflex control and spectral indicators of cardiac sympatho\u2010vagal balance. Furthermore, CSD improved protein and albuminuria, decreased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>evoked responses from stellate neurons, and also reduced indicators of brainstem inflammation. In summary, CSD in 2K1C rats reduces the hypertensive burden and improves renal function. This may be mediated by improvements in autonomic balance, functional remodelling of post\u2010ganglionic neurons and reduced inflammation. Our results suggest that the peripheral chemoreflex may be considered as a potential therapeutic target for controlling renovascular hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp272708","type":"journal-article","created":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T09:08:51Z","timestamp":1470906531000},"page":"6255-6266","source":"Crossref","is-referenced-by-count":45,"title":["Carotid sinus denervation ameliorates renovascular hypertension in adult Wistar rats"],"prefix":"10.1113","volume":"594","author":[{"given":"Wioletta","family":"Pijacka","sequence":"first","affiliation":[{"name":"School of Physiology, Pharmacology &amp; Neuroscience, Biomedical Sciences University of Bristol Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona D.","family":"McBryde","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology &amp; Neuroscience, Biomedical Sciences University of Bristol Bristol UK"},{"name":"Department of Physiology, Faculty of Medical and Health Sciences University of Auckland Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Marvar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology The George Washington University School of Medical and Health Sciences Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisele S.","family":"Lincevicius","sequence":"additional","affiliation":[{"name":"Cardiovascular Division \u2010 Department of Physiology, Escola Paulista de Medicina Universidade Federal de Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana P. 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