Effects of ouabain and flecainide on CO 2-induced slowly adapting pulmonary stretch receptor inhibition in the rabbit

Abstract

The inhibitory effect of CO 2 on slowly adapting pulmonary stretch receptors (SARs) was examined before and after administration of ouabain, a Na +7z.sbnd;K + ATPase inhibitor, and flecainide, a Na + channel blocker. The experiments were performed in anesthetized, artificially ventilated rabbits after vagus nerve section. CO 2 inhalation (maximal tracheal CO 2 concentration ranging from 9.2 % to 10.4 %) for about 60 sec decreased the receptor activity during both inflation and deflation. The magnitude of decreased SAR activity during deflation was greater than that seen during inflation. Administration of ouabain (25 μg/kg) initially stimulated SAR activities during inflation and deflation, and after 20 min, the SAR response was still kept excitatory in both inflation and deflation phases. Under these conditions, CO 2 inhalation inhibited SAR activities during inflation and deflation. Flecainide treatment (3 mg/kg) that abolished veratridine (30 μg/kg)-induced SAR excitation had no significant effect on the inhibitory responses of SAR activity to CO 2. These results suggest that the inhibitory effect of CO 2, occurs when ouabain results in intracellular Na + concentration ([Na +] i) increases in the SAR endings, and that CO 2-induced SAR inhibition may not be related to the reduction of influx of Na + through voltage-gated Na + channels.