{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:56:16Z","timestamp":1793692576161,"version":"4.5.1"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T00:00:00Z","timestamp":1377561600000},"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":[[2013,11]]},"abstract":"<jats:title>New findings<\/jats:title><jats:p><jats:list list-type=\"explicit-label\"><jats:list-item><jats:p><jats:bold>What is the central question of this study?\u2002<\/jats:bold><\/jats:p><jats:p>What mechanisms mediate chronic intermittent hypoxia\u2010induced increases in endothelin\u20101 in the carotid body?<\/jats:p><\/jats:list-item><jats:list-item><jats:p><jats:bold>What is the main finding and its importance?\u2002<\/jats:bold><\/jats:p><jats:p>Upregulation of endothelin\u20101 by chronic intermittent hypoxia results from reactive oxygen species\u2010dependent activation of endothelin\u2010converting enzyme and is not the result of augmented endothelin\u20101 gene transcriptional activity. The resultant increased endothelin\u20101 acts via endothelin\u20101A receptors to induce hypoxic hypersensitivity of the carotid body but does not contribute to the sensory long\u2010term facilitation observed in this condition. These findings provide mechanistic insight into how chronic intermittent hypoxia alters carotid body function.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><jats:p>Chronic intermittent hypoxia (CIH) leads to remodelling of the carotid body function, manifested by an augmented sensory response to hypoxia and induction of sensory long\u2010term facilitation (LTF). It was proposed that endothelin\u20101 (ET\u20101) contributes to CIH\u2010induced hypoxic hypersensitivity of the carotid body. The objectives of the present study were as follows: (i) to delineate the mechanisms by which CIH upregulates ET\u20101 expression in the carotid body; and (ii) to assess whether ET\u20101 also contributes to sensory LTF. Experiments were performed on adult, male rats exposed to alternating cycles of 5% O<jats:sub>2<\/jats:sub>(15 s) and room air (5 min), nine episodes per hour and 8 h per day for 10 days. Chronic intermittent hypoxia increased ET\u20101 levels in glomus cells without significantly altering prepro\u2010endothelin\u20101 mRNA levels. The activity of endothelin\u2010converting enzyme increased with concomitant elevation of ET\u20101 levels in CIH\u2010exposed carotid bodies, and MnTMPyP, a membrane\u2010permeable antioxidant, prevented these effects. Hypoxia facilitated ET\u20101 release from CIH\u2010treated carotid bodies, which is a prerequisite for activation of ET receptors; however, hypoxia had no effect on ET\u20101 release from control carotid bodies. In CIH\u2010exposed carotid bodies, mRNAs encoding ET<jats:sub>A<\/jats:sub>receptor were upregulated, and an ET<jats:sub>A<\/jats:sub>receptor\u2010specific antagonist abolished CIH\u2010induced hypersensitivity of the hypoxic response, whereas it had no effect on the sensory LTF. These results suggest that ECE\u2010dependent increased production of ET\u20101 coupled with hypoxia\u2010evoked ET\u20101 release and the ensuing ET<jats:sub>A<\/jats:sub>receptor activation mediate the CIH\u2010induced carotid body hypersensitivity to hypoxia, but the ET<jats:sub>A<\/jats:sub>signalling pathway is not associated with sensory LTF elicited by CIH.<\/jats:p>","DOI":"10.1113\/expphysiol.2013.073700","type":"journal-article","created":{"date-parts":[[2013,8,3]],"date-time":"2013-08-03T00:32:07Z","timestamp":1375489927000},"page":"1620-1630","source":"Crossref","is-referenced-by-count":47,"title":["Role of oxidative stress\u2010induced endothelin\u2010converting enzyme activity in the alteration of carotid body function by chronic intermittent 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