Heme oxygenase–carbon monoxide pathway is involved in regulation of respiration in medullary slice of neonatal rats

Carbon monoxide (CO) is a novel biological messenger molecule. It is well known that CO can be synthesized in mammalian cells. In addition, CO is also demonstrated to participate in many physiological processes, such as vasomotion, thermoregulation and respiratory regulation. The purpose of our present study was to investigate the role of heme oxygenase–carbon monoxide (HO–CO) pathway in central regulation of respiration. The experiments were carried out on the medullary slices of neonatal Sprague–Dawley rats. The discharge activity of the hypoglossal rootlets was recorded to indicate the central rhythmic respiratory activity and its duration (DD), interval (DI), frequency (DF) and integrated amplitude (IA) were analyzed. The slices were perfused with ZnPP-9 (a potent inhibitor of heme oxygenase), CO and hemin (substrate of heme oxygenase), respectively, to observe their effects on respiratory activity. The results obtained were as follows: ZnPP-9 could decrease DD, DI and IA, and increase DF (P < 0.05); exogenous CO caused a decrease in DD and DF, and an increase in DI and IA (P < 0.05); in response to hemin, DI and IA decreased, DF increased (P < 0.05), and DD did not change significantly (P > 0.05); administration of both ZnPP-9 and hemin could decrease DI, and increase DF (P < 0.05), but did not affect DD and IA significantly (P > 0.05). It can be concluded from the results above that the HO–CO pathway may be involved in the regulation of rhythmic respiration at the level of medulla oblongata.