title: Transient carbon monoxide inhibits the ventilatory responses to hypoxia through peripheral mechanisms in the rat.
abstract: Hypoxia inhibits K+ channels of chemoreceptors of the carotid body (CB), which is reversed by transient carbon monoxide (CO), suggesting an inhibitory effect of CO on hypoxic stimulation of carotid chemoreceptors. Therefore, we hypothesized that the ventilatory responses to hypoxic stimulation of the CB might be depressed in intact rats by transient inhalation of CO. Anesthetized, spontaneously breathing rats were exposed to room air, and 1 min of 11% O2 (HYP) and CO (0.25-2%) alone and in combination (HYP+CO). We found that transient CO did not affect baseline cardiorespiratory variables, but significantly attenuated hypoxic ventilatory augmentation, predominantly via reduction of tidal volume. To distinguish whether this CO modulation occurs at the CB or within the central nervous system, the cardiorespiratory responses to electrical stimulation of the fastigial nucleus (FN), a cerebellar nucleus known excitatory to respiration, were compared before and during transient CO. Our results showed that the FN-mediated cardiorespiratory responses were not significantly changed by transient CO exposure. To evaluate the effect of CO accumulation, we also compared baseline cardiorespiratory responses to 5 min of 1% and 2% CO, respectively. Interestingly, only the latter produced a biphasic ventilatory response (initial increase followed by decrease) associated with hypotension. We conclude that eupneic breathing in anesthetized rat was not affected by transient CO, but was altered by prolonged exposure to higher levels of CO. Moreover, transient CO depresses hypoxic ventilatory responses mainly through peripherally inhibiting hypoxic stimulation of carotid chemoreceptors.
authors.affiliation: Department of Pathophysiology, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhuang
authors.forename: Fadi
authors.initials: F
authors.lastname: Xu
authors.forename: Matthew
authors.initials: M
authors.lastname: Campen
authors.forename: Joseph
authors.initials: J
authors.lastname: Hernandez
authors.forename: Shan
authors.initials: S
authors.lastname: Shi
authors.forename: Rurong
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002249:Carbon Monoxide Poisoning / Q000503:physiopathology*; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000503:physiopathology; D012123:Pulmonary Ventilation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects* / Q000503:physiopathology; D013990:Tidal Volume / Q000187:drug effects / Q000502:physiology