Flecainide inhibits the stimulatory effect of veratridine on the response of airway mechanoreceptors to maintained inflations in rats

Abstract

Aims: the purpose of the present study was to investigate (a) whether maintained inflations result in the inhibition of slowly adapting pulmonary stretch receptor (SAR) discharge to elicit an abrupt change in receptor activity and (b) whether pretreatment with veratridine, a Na(+) channel opener, and/or flecainide, a Na(+) channel blocker, alters the responses of SAR properties to maintained inflations.

Main methods: we measured the properties of SAR activity during maintained inflations at different pressures in 31 anesthetized, artificially ventilated rats with unilateral vagotomy.

Key findings: During maintained inflations (approximately 5, 10 and 15 cmH(2)O) for about 5s, the procedures did not produce the induction of inhibition of either 16 low-threshold SARs (firing during both inflation and deflation) or 15 high-threshold SARs (firing during inflation only). In these preparations, the excitatory responses of SARs to maintained inflations at three different pressures were markedly enhanced after administration of veratridine (50 μg/kg), but under such conditions, the inhibition of SAR discharges was not observed. In the same SAR preparations, after flecainide treatment (9 mg/kg) sufficient for the blockade of veratridine (50 μg/kg)-induced SAR stimulation, maintained inflations at higher pressures (10 and 15 cmH(2)O) greatly inhibited SAR discharges. Under these conditions, the inhibition of SAR discharges was not observed during maintained inflations at 5 cmH(2)O.

Significance: These results suggest that neither low-threshold SARs nor high-threshold SARs in the rat lung are deactivated during maintained inflations at higher pressures.