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The retrotrapezoid nucleus is a crucial hub for CO<jats:sub>2<\/jats:sub> chemosensitivity; its ablation or inhibition attenuates CO<jats:sub>2<\/jats:sub> chemoreflexes and diminishes restful breathing. Similar phenotypes characterize certain hypoventilation syndromes, suggesting underlying retrotrapezoid nucleus impairment in these disorders. Progesterone stimulates restful breathing and CO<jats:sub>2<\/jats:sub> chemoreflexes. However, its mechanisms and sites of actions remain unknown and the experimental use of synthetic progestins in patients and animal models have been met with mixed respiratory outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could rescue respiratory chemoreflexes following selective lesion of the retrotrapezoid nucleus with saporin toxin. Adult female Sprague Dawley rats were grouped based on lesion size determined by the number of surviving chemosensitive neurons, and ventilatory responses were measured by whole body plethysmography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ventilatory responses to hypercapnia (but not hypoxia) were compromised in a lesion\u2010dependent manner. Chronic etonogestrel treatment improved CO<jats:sub>2<\/jats:sub> chemosensitivity selectively in rats with moderate lesion, suggesting that a residual number of chemosensitive neurons are required for etonogestrel\u2010induced CO<jats:sub>2<\/jats:sub> chemoreflex recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study provides new evidence for the use of progestins as respiratory stimulants under conditions of central hypoventilation and provides a new testable model for assessing the mechanism of action of progestins in the respiratory network.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.14093","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T11:29:37Z","timestamp":1706009377000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Etonogestrel promotes respiratory recovery in an in\u00a0vivo rat model of central chemoreflex 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