{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T03:38:23Z","timestamp":1773459503826,"version":"3.50.1"},"reference-count":37,"publisher":"Bentham Science Publishers Ltd.","issue":"1","content-domain":{"domain":["opencardiovascularmedicinejournal.com","benthamopen.com"],"crossmark-restriction":true},"short-container-title":["TOCMJ"],"published-print":{"date-parts":[[2007,6,11]]},"abstract":"Hypoxia regulates the local expression of angiotensin-generating system in the rat carotid body and the me-tabolite angiotensin IV (Ang IV) may be involved in the modulation of carotid body function. We tested the hypothesis that Ang IV-binding angiotensin AT4<\/jats:sub> receptors play a role in the adaptive change of the carotid body in hypoxia. The expression and localization of Ang IV-binding sites and AT4<\/jats:sub> receptors in the rat carotid bodies were studied with histochemistry. Specific fluorescein-labeled Ang IV binding sites and positive staining of AT4<\/jats:sub> immunoreactivity were mainly found in lobules in the carotid body. Double-labeling study showed the AT4<\/jats:sub> receptor was localized in glomus cells containing tyrosine hydroxylase, suggesting the expression in the chemosensitive cells. Intriguingly, the Ang IV-binding and AT4<\/jats:sub> immunoreactivity were more intense in the carotid body of chronically hypoxic (CH) rats (breathing 10% oxygen for 4 weeks) than the normoxic (Nx) control. Also, the protein level of AT4<\/jats:sub> receptor was doubled in the CH comparing with the Nx group, supporting an upregulation of the expression in hypoxia. To examine if Ang IV induces intracellular Ca2+<\/jats:sup> response in the carotid body, cytosolic calcium ([Ca2+<\/jats:sup>]i<\/jats:sub>) was measured by spectrofluorimetry in fura-2-loaded glomus cells dissociated from CH and Nx carotid bodies. Exogenous Ang IV elevated [Ca2+<\/jats:sup>]i<\/jats:sub> in the glomus cells and the Ang IV response was significantly greater in the CH than the Nx group. Hence, hypoxia induces an upregulation of the expression of AT4<\/jats:sub> receptors in the glomus cells of the carotid body with an increase in the Ang IV-induced [Ca2+<\/jats:sup>]i elevation. This may be an additional pathway enhancing the Ang II action for the activation of chemoreflex in the hypoxic response during chronic hypoxia.<\/jats:p>","DOI":"10.2174\/1874192400701010001","type":"journal-article","created":{"date-parts":[[2007,12,19]],"date-time":"2007-12-19T12:02:15Z","timestamp":1198065735000},"page":"1-7","update-policy":"https:\/\/doi.org\/10.2174\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Carotid Body AT4 Receptor Expression and its Upregulation in Chronic Hypoxia"],"prefix":"10.2174","volume":"1","author":[{"given":"Man-Lung","family":"Fung","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siu-Yin","family":"Lam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tung-Po","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung-Wui","family":"Tjong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Sing","family":"Leung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","reference":[{"key":"refR1","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1152\/physrev.1994.74.4.829","volume":"74","author":"Gonzalez C","year":"1994","unstructured":"Gonzalez C, Almaraz L, Obeso A, Rigual R. \n Carotid body chemoreceptors: from natural stimuli to sensory discharges \n Physiol Rev \n 1994; 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