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Tidal volume (<jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>), breathing frequency (<jats:italic>f<\/jats:italic><jats:sub>b<\/jats:sub>)and rate of rise of diaphragm EMG were increased in 6 of 7 dogs but did not achieve statistical significance.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We propose that hyperaddition is the dominant form of chemoreceptor interaction under conditions of quiet wakefulness in intact animals and over a wide range of CB <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp6779-math-0002.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp6779:tjp6779-math-0002\"\/>and <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp6779-math-0003.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp6779:tjp6779-math-0003\"\/>.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>We asked if the type of carotid body (CB) chemoreceptor stimulus influenced the ventilatory gain of the central chemoreceptors to CO<jats:sub>2<\/jats:sub>. The effect of CB normoxic hypocapnia, normocapnia and hypercapnia (carotid body <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp6779-math-0004.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp6779:tjp6779-math-0004\"\/>\u00a0\u2248\u00a022, 41 and 68\u00a0mmHg, respectively) on the ventilatory CO<jats:sub>2<\/jats:sub> sensitivity of central chemoreceptors was studied in seven awake dogs with vascularly\u2010isolated and extracorporeally\u2010perfused CBs. Chemosensitivity with one CB was similar to that in intact dogs. In four CB\u2010denervated dogs, absence of hyper\u2010\/hypoventilatory responses to CB perfusion with <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp6779-math-0005.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp6779:tjp6779-math-0005\"\/> of 19\u201375\u00a0mmHg confirmed separation of the perfused CB circulation from the brain. The group mean central CO<jats:sub>2<\/jats:sub> response slopes were increased 303% for minute ventilation (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp6779-math-0006.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp6779:tjp6779-math-0006\"\/>)(<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.01) and 251% for mean inspiratory flow rate (<jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>\/<jats:italic>T<\/jats:italic><jats:sub>I<\/jats:sub>) (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.05) when the CB was hypercapnic <jats:italic>vs<\/jats:italic>. hypocapnic; central CO<jats:sub>2<\/jats:sub> response slopes for tidal volume (<jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>), breathing frequency (<jats:italic>f<\/jats:italic><jats:sub>b<\/jats:sub>) and rate of rise of the diaphragm EMG increased in 6 of 7 animals but the group mean changes did not reach statistical significance. Group mean central CO<jats:sub>2<\/jats:sub> response slopes were also increased 237% for <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp6779-math-0007.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp6779:tjp6779-math-0007\"\/>(<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.01) and 249% for <jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>\/<jats:italic>T<\/jats:italic><jats:sub>I<\/jats:sub>(<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.05) when the CB was normocapnic <jats:italic>vs<\/jats:italic>. hypocapnic, but no significant differences in any of the central ventilatory response indices were found between CB normocapnia and hypercapnia. These hyperadditive effects of CB hyper\u2010\/hypocapnia agree with previous findings using CB hyper\u2010\/hypoxia.We propose that hyperaddition is the dominant form of chemoreceptor interaction in quiet wakefulness when the chemosensory control system is intact, response gains physiological, and carotid body chemoreceptors are driven by a wide range of O<jats:sub>2<\/jats:sub> and\/or CO<jats:sub>2<\/jats:sub>.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp270114","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T17:12:20Z","timestamp":1436893940000},"page":"4225-4243","source":"Crossref","is-referenced-by-count":93,"title":["Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO<sub>2<\/sub>: role of carotid body CO<sub>2<\/sub>"],"prefix":"10.1113","volume":"593","author":[{"given":"Curtis. 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