Role Of SGC-cGMP Pathway In CO-mediated Central Regulation Of Respiration

The aim of our present research is to investigate if the soluble guanylyl cyclase-cyclic guanine monophosphate (sGC-cGMP) pathway participates in carbon monoxide (CO) mediated regulation of respiration at the level of medulla oblongata. The electrophysiological recordings and the radioimmunoassay (RIA) were carried out in the medullary slices of newborn Sprague-Dawley rats, to investigate the role of the sGC-cGMP pathway in the CO-mediated central regulation of respiration.1. Eiectrophysiological experimentsThis part is constituted of five groups (n=8/group): ACSF (artificial cerebrospinal fluid) control group, exogenous CO group, ODQ (1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-l-one, specific inhibitor of sGC) group, ODQ+CO group and DMSO (dimethyl sulfoxide, vehicle of ODQ) group. The burst duration (BD), burst interval (BI), burst frequency (BF) and integrated amplitude (IA) of burst of hypoglossal rootlets were taken as indexes of rhythmic respiratory activity. The slices were perfused with drugs above, respectively, to observe the change of respiratory activity. The results obtained were as follows.1) Effect of exogenous CO on hypoglossal rootlets dischargeIn exogenous CO group, comparing to the pre-control, BD decreased, BI increased, BF decreased and IA increased (P＜0.05). Comparing to the ACSF group, BD decreased, BI increased, BF decreased and IA increased (P＜0.05).2) Effect of OI)Q on hypoglossal rootlets dischargeIn ODQ group, comparing to the pre-control, BD and BI decreased, BF increased and IA decreased (P＜0.05). Comparing to the DMSO group, BD and BI decreased, BF increased (P＜0.05), IA showed no significant change (P＞0.05).3) Effect of combined application of ODQ and CO on hypoglossal rootlets dischargeIn ODQ group, comparing to the pre-control, BD and BI decreased, BF increased (P＜0.05), IA showed no significant change (P＞0.05). Comparing to the DMSO group, BD increased, BI decreased, BF and IA increased (P＜0.05). Comparing to the CO group, BD increased, BI decreased, BF increased, IA decreased (P＜0.05). Comparing to the ODQ group, BD and BI increased, BF decreased, IA increased (P＜0.05).4) Effeet of DMSO on hypoglossal rootlets dischargeIn ODQ group, comparing to the pre-control, BD, BI and BF showed no significant changes (P＞0.05), IA decreased (P＜0.05). Comparing to the ACSF group, BD did not change significantly (P＞0.05), BI decreased (P＜0.05), BF and IA showed no significant changes (P＞0.05).2. RIA of cGMP levelFour groups (n=6/group) were included in this part. ACSF control group, exogenous CO group, ODQ group and ODQ+CO group. The slices were taken immediately after drug application, homogenized and precipitated, and the supematant was taken to measure the cGMP level by RIA Kit. The results obtained were as follows. The cGMP level of the slices could be increased by exogenous CO (P＜0.01), but decreased by ODQ (P＜0.05), comparing to the ACSF group. When ODQ and CO were applied simultaneously, cGMP level did not change significantly (P＞0.05).These results indicate that CO could decrease the respiratory frequency by lengthening the expiratory duration and increase the inspiratory amplitude. sGC's specific inhibitor ODQ could increase the respiratory frequency by shortening the inspiratory duration and expiratory duration. The changes of rhythmic respiratory activity were consistent to the altering of the cGMP level. It can be concluded that sGC-cGMP pathway may play an important role in the CO mediated regulation of respiration at the level of medulla oblongata.