Effects of Acetazolamide and 4-Aminopyridine on CO2-induced Slowly Adapting Pulmonary Stretch Receptor Inhibition in Rats.

Inhibitory responses of slowly adapting pulmonary stretch receptor (SAR) activity to CO2 inhalation (maximal tracheal CO2 concentration ranging from 9.5 to 12.5%) for ∼60 s were examined before and after administration of acetazolamide (a carbonic anhydrase inhibitor) or 4-aminopyridine (4-AP, a K+ channel blocker). The experiments were performed in 35 anesthetized, artifically ventilated rats after unilateral vagotomy. Sixty-eight of eighty-four SARs were inhibited by CO2 inhalation. The SAR inhibition was attenuated by pretreatment with either acetazolamide (20 mg/kg, n = 10) or 4-AP (0.7 and 2.0 mg/kg, n = 10). In other series of experiments, stainings to show the existence of carbonic anhydrase (CA) enzymatic reaction were not found in the smooth muscle of either extrapulmonary or intrapulmonary bronchi. Protein gene product 9.5 (PGP 9.5)-immunoreactive SAR terminals to form leaflike extensions were found in the bronchioles at different diameters and were smooth-muscle-related receptors. But in the same sections, CA isozyme II-like (erythrocyte CA) immunoreactive SAR terminals were not identified. These results suggest that CO2-induced inhibition of SARs may be involved in the CA-dependent CO2 hydration in addition to the activation of 4-AP sensitive K+ currents. [ABSTRACT FROM AUTHOR]