RESPIRATORY EFFECTS OF KYNURENIC ACID MICROINJECTED INTO THE VENTROMEDULLARY SURFACE OF THE RAT

Several studies demonstrate that, within the ventral medullary surface (VMS), excitatory amino acids are necessary components of the neural circuits involved in the tonic and reflex control of respiration and c irculation. In the present study we investigated the cardiorespiratory effects of unilateral microinjections of the broad spectrum glutamate antagonist kynurenic acid (2 nmol/200 nl) along the VMS of urethane-a nesthetized rats. Within the VMS only one region was responsive to thi s drug. This area includes most of the intermediate respiratory area, partially overlapping the rostral ventrolateral medulla (IA/RVL). When microinjected into the IA/RVL, kynurenic acid produced a respiratory depression, without changes in mean arterial pressure or heart rate. T he respiratory depression observed was characterized by a decrease in ventilation, tidal volume and mean inspiratory flow and an increase in respiratory frequency. Therefore, the observed respiratory depression was entirely due to a reduction in the inspiratory drive. Microinject ions of vehicle (200 nl of saline) into this area produced no signific ant changes in breathing pattern, blood pressure or heart rate. Respir atory depression in response to the blockade of glutamatergic receptor s inside the rostral VMS suggests that neurons at this site have an en dogenous glutamatergic input controlling the respiratory cycle duratio n and the inspiratory drive transmission.