Involvement of nitric oxide in realization of the NMDA influence on the respiratory rhythm generated by medullo-spinal preparations of early postnatal rats

Abstract

The effects of blocking of NO synthase on the dynamics of NMDA-induced changes in the respiratory activity were studied in experiments on semi-isolated in situ medullo-spinal preparations of 3-lo 4-day-old rats. The experiments were carried out with the ventroiateral regions of the medulla (VLMR) left intact or when the rostral portion of this region (corresponding to the chemce, ensitive zone M) had been separated by a transversial transection. Three-rain-long application of 5.0/aM NMDA increased the frequency of inspiratory discharges (ID); the shifts were more intensive after separation of the VLM rostral portion. Superfusion of preparations with a solution containing 10.0 aM of an NO synthase inhibitor, methyl ester of N6-nitro-L-arginine (MENA), increased the frequency and decreased the amplitude and integral intensity of ID generated by the preparations with the intact VIAl, whereas after separation of the rostral VLM portion this inhibitor decreased the ID frequency. Application of 5 #M NMDA against the background of 10-rain-long superfusion with the 10 pM MENA-containing solution resulted in no significant increase in the ID frequency. Mter the rostral VLM portion had been removed, NMDA application after superfnsion with the MENA-containing solution led to frequency shifts, which did not significantly differ from tho~e in the absence of the blockade of NO synthase. Against the MENA influence, NMDA-induced depression of the ID amplitude became significantly more intensive. The experiments showed that during the early postnatal period endogenous NO is involved in realization of the NMDA influence on the parameters of respiratory activity of rats. Possible mechanisms of the influences exerted by activation of NMDA receptors and by the associated NO synthesis on regulation of the respiratory rhythmogenesis and their specificity within the early postnatal period are discussed.