{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:04:13Z","timestamp":1782345853578,"version":"3.54.5"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,12,23]],"date-time":"2018-12-23T00:00:00Z","timestamp":1545523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM 104357"],"award-info":[{"award-number":["P20 GM 104357"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["U54 GM115428"],"award-info":[{"award-number":["U54 GM115428"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>We previously demonstrated that central nervous system (CNS) melanocortin 4 receptors (MC4R) play a key role in regulating blood pressure (BP) in some conditions associated with increased SNS activity, including obesity. In this study, we examined whether activation of CNS MC4R contributes to chronic intermittent hypoxia (CIH)\u2010induced hypertension and ventilatory responses to hypercapnia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rats were instrumented with an intracerebroventricular (ICV) cannula in the lateral cerebral ventricle for continuous infusion of MC4R antagonist (SHU\u20109119) and telemetry probes for measuring mean arterial pressure (MAP) and heart rate (HR). Untreated and SHU\u20109119\u2010treated rats as well as obese and lean MC4R\u2010deficient rats were exposed to CIH for 7\u201018 consecutive days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chronic intermittent hypoxia reduced cumulative food intake by 18\u00a0\u00b1\u00a05\u00a0g while MAP and HR increased by 10\u00a0\u00b1\u00a03\u00a0mm\u00a0Hg and 9\u00a0\u00b1\u00a05\u00a0bpm in untreated rats. SHU\u20109119 increased food intake (from 15\u00a0\u00b1\u00a01 to 46\u00a0\u00b1\u00a03\u00a0g) and prevented CIH\u2010induced reduction in food intake. CIH\u2010induced hypertension was not attenuated by MC4R antagonism (average increase of 10\u00a0\u00b1\u00a01 vs 9\u00a0\u00b1\u00a01\u00a0mm\u00a0Hg for untreated and SHU\u20109119 treated rats). In obese MC4R\u2010deficient rats, CIH for 7\u00a0days raised BP by 11\u00a0\u00b1\u00a04\u00a0mm\u00a0Hg. However, when MC4R\u2010deficient rats were food restricted to prevent obesity, CIH\u2010induced hypertension was attenuated by 32%. We also found that MC4R deficiency was associated with impaired ventilatory responses to hypercapnia independently of obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results show that obesity and the CNS melanocortin system interact in complex ways to elevate BP during CIH and that MC4R may be important in the ventilatory responses to hypercapnia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13222","type":"journal-article","created":{"date-parts":[[2018,11,22]],"date-time":"2018-11-22T17:54:53Z","timestamp":1542909293000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Role of melanocortin 4 receptor in hypertension induced by chronic intermittent hypoxia"],"prefix":"10.1111","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0471-0512","authenticated-orcid":false,"given":"Jussara M.","family":"do Carmo","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular\u2010Renal Research Center University of Mississippi Medical Center Jackson Mississippi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre A.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular\u2010Renal Research Center University of Mississippi Medical Center Jackson Mississippi"},{"name":"Bar\u00e3o de Mau\u00e1 University Center Ribeir\u00e3o Preto Brazil"},{"name":"Universidade Estadual de Minas Gerais Passos Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney P.","family":"Moak","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular\u2010Renal Research Center University of Mississippi Medical Center Jackson 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