{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:39:19Z","timestamp":1781188759214,"version":"3.54.1"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,10,23]],"date-time":"2013-10-23T00:00:00Z","timestamp":1382486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p><jats:p>Expression of the renin\u2013angiotensin system (RAS) may play a pathogenic role in the augmented activity of carotid body chemosensitive cells and the carotid body (CB) inflammation in chronic intermittent hypoxia (IH). The aim of this study was to examine the expression and function of the RAS components in the CB during chronic IH resembling a severe sleep\u2010apnoeic condition.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p><jats:p>Chronic IH induces a functional upregulation of the RAS expression in the CB. The upregulation of RAS expression could play a pathogenic role in the augmented CB excitability during IH, which is relevant to early pathogenesis in sleep\u2010disordered breathing.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>The carotid body (CB) plays an important role in the alteration of cardiorespiratory activity in chronic intermittent hypoxia (IH) associated with sleep\u2010disordered breathing, which may be mediated by local expression of the renin\u2013angiotensin system (RAS). We hypothesized a pathogenic role for IH\u2010induced RAS expression in the CB. The CB expression of RAS components was examined in rats exposed to IH resembling a severe sleep\u2010apnoeic condition for 7 days. <jats:italic>In situ<\/jats:italic> hybridization showed an elevated expression of angiotensinogen in the CB glomus cells in the hypoxic group when compared with the normoxic control group. Immunohistochemical studies and Western blot analysis revealed increases in the protein level of both angiotensinogen and angiotensin II type 1 (AT<jats:sub>1<\/jats:sub>) receptors in the hypoxic group, which were localized to the glomic clusters containing tyrosine hydroxylase. RT\u2010PCR studies confirmed that levels of the mRNA expression of angiotensinogen, angiotensin\u2010converting enzyme, AT<jats:sub>1a<\/jats:sub> and AT<jats:sub>2<\/jats:sub> receptors were significantly increased in the CBs of the hypoxic rats. Functionally, the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> response to exogenous angiotensin II was enhanced in fura\u20102\u2010loaded glomus cells dissociated from hypoxic rats when compared with those of the normoxic control animals. Pretreatment with losartan, but not PD123319, abolished the angiotensin II\u2010induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> response, suggesting an involvement of AT<jats:sub>1<\/jats:sub> receptors. Moreover, daily treatment of the IH group of rats with losartan attenuated the levels of oxidative stress, gp91<jats:sup>phox<\/jats:sup> expression and macrophage infiltration in the CB. Collectively, the upregulated local RAS expression could play a pathogenic role in the augmented CB activity and local inflammation via AT<jats:sub>1<\/jats:sub> receptor activation during IH conditions in patients with sleep\u2010disordered breathing.<\/jats:p>","DOI":"10.1113\/expphysiol.2013.074591","type":"journal-article","created":{"date-parts":[[2013,9,14]],"date-time":"2013-09-14T04:22:31Z","timestamp":1379132551000},"page":"220-231","source":"Crossref","is-referenced-by-count":64,"title":["Upregulation of a local renin\u2013angiotensin system in the rat carotid body during chronic intermittent 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