ABSTRACT
OBJECTIVE: To identify the role of soluble guanylyl cyclase-cyclic guanine monophosphate (sGC-cGMP) pathway in the carbon monoxide (CO) mediating regulation of respiratory rhythm from the medulla oblongata. METHODS: Medullary slices of newborn Sprague-Dawley rats were prepared for the experiment. The electrophysiological experiment comprised 5 groups (each with 8 slices), each of which were perfused with artificial cerebrospinal fluid (ACSF control group), CO (exogenous CO group), 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (a specific inhibitor of sGC, ODQ group), ODQ+CO (ODQ+CO group), and dimethyl sulfoxide (vehicle of ODQ, DMSO group), respectively. The burst frequency (BF) of hypoglossal rootlets was recorded as an index of rhythmic respiratory activity. Radioimmunoassay was employed to determine cGMP levels of the medullary slices of the ACSF control group, exogenous CO group, ODQ group and ODQ+CO group (n=6/ group). RESULTS: The exogenous CO decreased the BF (P < 0.05) and increased the cGMP level (P < 0.05). The ODQ increased the BF (P < 0.05) and decreased the cGMP level (P < 0.05). No significant changes were found in the BF and cGMP levels when CO and ODQ applied simultaneously (P > 0.05), but the BF increased (P < 0.05) after the drug perfusion ended. CONCLUSION: sGC-cGMP pathway may play an important role in the CO mediated regulation of respiratory rhythm from the medulla oblongata.
Subject(s)
Carbon Monoxide/pharmacology , Cyclic GMP/metabolism , Guanylate Cyclase/metabolism , Periodicity , Receptors, Cytoplasmic and Nuclear/metabolism , Respiration/drug effects , Signal Transduction/drug effects , Animals , Animals, Newborn , Electrophysiological Phenomena/drug effects , Female , Hypoglossal Nerve/drug effects , Hypoglossal Nerve/metabolism , Hypoglossal Nerve/physiology , In Vitro Techniques , Male , Medulla Oblongata/drug effects , Medulla Oblongata/metabolism , Medulla Oblongata/physiology , Rats , Rats, Sprague-Dawley , Soluble Guanylyl CyclaseABSTRACT
The aim of the present study was to investigate the effect of endogenous carbon monoxide (CO) on respiratory rhythm. The experiments were carried out on the medullary slices of newborn Sprague-Dawley rats. The rhythmic discharge frequency (DF) of hypoglossal rootlets was taken as an index of rhythmic respiratory activity. The slices of medulla oblongata were superfused with ZnPP-9 (inhibitor of heme oxygenase), CO and hemin (substrate of heme oxygenase), respectively, to observe their effects on respiratory rhythm. The preparations were divided into 5 groups: control group of artificial cerebrospinal fluid (ACSF), group of ZnPP-9, group of exogenous CO, group of hemin and group of ZnPP-9 + hemin. The results obtained were as follows. In ZnPP-9 group, the rhythmic DF of the hypoglossal rootlets was increased (P<0.05); while in exogenous CO group, it was decreased (P<0.05). In the groups of hemin and ZnPP-9 + hemin, the rhythmic DF of the hypoglossal rootlets was increased (P<0.05). It is suggested that endogenous CO may play an important role in the regulation of respiratory rhythm.
