Substance P antagonist does not block the stimulation of rapidly adapting pulmonary stretch receptors by ammonia.

We investigated the effects of the substance P (SP) blocker [D-Pro2,D-Trp7,9]-SP on the response of rapidly adapting pulmonary stretch receptors (RARs) to SP administered into the right atrium, or ammonia vapor inhaled into the lungs in anesthetized, spontaneously breathing rabbits. Right atrial administration of SP (0.3, 1.0, and 3.0 micrograms/kg) caused an increase in the RAR activity, and this increase became more prominent as the dose of SP was increased. The RARs increased their activity following inhalation of vapor from 5 and 10% ammonia solutions, and the increase was concentration dependent. The excitatory responses of RAR activity to SP at different doses were greatly diminished or completely blocked by administration of the selective SP antagonist (300 and 500 micrograms/kg). However, the ammonia-induced RAR stimulation was not significantly altered by prior treatment with the SP blocker (300 and 500 micrograms/kg). These results suggest that the stimulation of RARs by ammonia does not occur as a result of the release of SP from sensory nerves in the airways and lungs.