{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:46:24Z","timestamp":1777538784780,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>There is evidence that H<jats:sub>2<\/jats:sub>S plays a role in the control of breathing: what are its actions on the ventilatory and thermoregulatory responses to hypercapnia via effects in the medullary raphe, a brainstem region that participates in the ventilatory adjustments to hypercapnia?<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Hypercapnia increased the endogenous production of H<jats:sub>2<\/jats:sub>S in the medullary raphe. Inhibition of endogenous H<jats:sub>2<\/jats:sub>S attenuated the ventilatory response to hypercapnia in unanaesthetized rats, suggesting its excitatory action via the cystathionine \u03b2\u2010synthase\u2013H<jats:sub>2<\/jats:sub>S pathway in the medullary raphe.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) has been recently recognized as a gasotransmitter alongside carbon monoxide (CO) and nitric oxide (NO). H<jats:sub>2<\/jats:sub>S seems to modulate the ventilatory and thermoregulatory responses to hypoxia and hypercapnia. However, the action of the H<jats:sub>2<\/jats:sub>S in the medullary raphe (MR) on the ventilatory responses to hypercapnia remains to be elucidated. The present study aimed to assess the role of H<jats:sub>2<\/jats:sub>S in the MR (a brainstem region that contains CO<jats:sub>2<\/jats:sub>\u2010sensitive cells and participates in the ventilatory adjustments to hypercapnia) in the ventilatory responses to hypercapnia in adult unanaesthetized Wistar rats. To do so, aminooxyacetic acid (AOA; a cystathionine \u03b2\u2010synthase (CBS) enzyme inhibitor), propargylglycine (PAG; a cystathionine \u03b3\u2010lyase enzyme inhibitor) and sodium sulfide (Na<jats:sub>2<\/jats:sub>S; an H<jats:sub>2<\/jats:sub>S donor) were microinjected into the MR. Respiratory frequency (<jats:italic>f<\/jats:italic><jats:sub>R<\/jats:sub>), tidal volume (<jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>), ventilation (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/eph13044-math-0001.png\" xlink:title=\"urn:x-wiley:09580670:media:eph13044:eph13044-math-0001\"\/>), oxygen consumption (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/eph13044-math-0002.png\" xlink:title=\"urn:x-wiley:09580670:media:eph13044:eph13044-math-0002\"\/>) and body temperature (<jats:italic>T<\/jats:italic><jats:sub>b<\/jats:sub>) were measured under normocapnic (room air) and hypercapnic (7% CO<jats:sub>2<\/jats:sub>) conditions. H<jats:sub>2<\/jats:sub>S concentration within the MR was determined. Microinjection of the drugs did not affect <jats:italic>f<\/jats:italic><jats:sub>R<\/jats:sub>, <jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub> and <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/eph13044-math-0003.png\" xlink:title=\"urn:x-wiley:09580670:media:eph13044:eph13044-math-0003\"\/> during normocapnia when compared to the control group. However, the microinjection of AOA, but not PAG, attenuated <jats:italic>f<\/jats:italic><jats:sub>R<\/jats:sub> and <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/eph13044-math-0004.png\" xlink:title=\"urn:x-wiley:09580670:media:eph13044:eph13044-math-0004\"\/> during hypercapnia in comparison to the vehicle group, but had no effects on <jats:italic>T<\/jats:italic><jats:sub>b<\/jats:sub>. In addition, we observed an increase in the endogenous production of H<jats:sub>2<\/jats:sub>S in the MR during hypercapnia. Our findings indicate that endogenously produced H<jats:sub>2<\/jats:sub>S in the MR plays an excitatory role in the ventilatory response to hypercapnia, acting through the CBS\u2013H<jats:sub>2<\/jats:sub>S pathway.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep089335","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T04:33:40Z","timestamp":1624422820000},"page":"1992-2001","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Role of hydrogen sulfide in ventilatory responses to hypercapnia in the medullary raphe of adult rats"],"prefix":"10.1113","volume":"106","author":[{"given":"Jo\u00e3o Paulo Jacob","family":"Sabino","sequence":"first","affiliation":[{"name":"Department of Biophysics and Physiology Graduate Program in Pharmaceutical Sciences Federal University of Piaui  Teresina PI Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas Vaz de Castro","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Physiology Graduate Program in Pharmaceutical Sciences Federal University of Piaui  Teresina PI Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3295-8120","authenticated-orcid":false,"given":"Renato Nery","family":"Soriano","sequence":"additional","affiliation":[{"name":"Division of Physiology and Biophysics Department of Basic Life Sciences Federal University of Juiz de Fora  Governador Valadares MG Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo","family":"Kwiatkoski","sequence":"additional","affiliation":[{"name":"Federal University of Mato Grosso do Sul  Tr\u00eas Lagoas MS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0292-4947","authenticated-orcid":false,"given":"Luiz G. S.","family":"Branco","sequence":"additional","affiliation":[{"name":"Department of Morphology, Physiology and Basic Pathology Dental School of Ribeirao Preto University of Sao Paulo  Ribeirao Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6269-7443","authenticated-orcid":false,"given":"Glauber S. 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