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A similar mechanism eliciting ventilatory stimulation in other vertebrate classes has been demonstrated, but it remains to be thoroughly investigated. Here, we investigated the effects of lactate ions on the cardiorespiratory system in swimming rainbow trout by manipulating the blood lactate concentration. Lactate elicited a vigorous, dose-dependent elevation of ventilation and bradycardia at physiologically relevant concentrations at constant pH. After this initial confirmation, we examined the chiral specificity of the response and found that only l-lactate induced these effects. By removal of the afferent inputs from the first gill arch, the response was greatly attenuated, and a comparison of the responses to injections up- and downstream of the gills collectively demonstrated that the lactate response was initiated by branchial cells. Injection of specific receptor antagonists revealed that a blockade of serotonergic receptors, which are involved in the hypoxic ventilatory response, significantly reduced the lactate response. Finally, we identified two putative lactate receptors based on sequence homology and found that both were expressed at substantially higher levels in the gills. We propose that lactate ions modulate ventilation by stimulating branchial oxygen-sensing cells, thus eliciting a cardiorespiratory response through receptors likely to have originated early in vertebrate evolution.<\/jats:p>","DOI":"10.1152\/ajpregu.00395.2018","type":"journal-article","created":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T21:01:08Z","timestamp":1551301268000},"page":"R607-R620","source":"Crossref","is-referenced-by-count":14,"title":["Effects of lactate ions on the cardiorespiratory system in rainbow trout (<i>Oncorhynchus mykiss<\/i>)"],"prefix":"10.1152","volume":"316","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6515-675X","authenticated-orcid":false,"given":"Mikkel T.","family":"Thomsen","sequence":"first","affiliation":[{"name":"Department of Bioscience, Zoophysiology, Aarhus University, Aarhus, 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