title: Effects of acetazolamide and 4-aminoprydine on the responses of deflationary slowly adapting pulmonary stretch receptors to CO2 inhalation in the rat.
abstract: The inhibitory effect of CO(2) on deflationary slowly adapting pulmonary stretch receptors (deflationary SARs) was investigated before and after administration of acetazolamide, a carbonic anhydrase (CA) inhibitor, or 4-aminopyridine (4-AP), a K(+) channel blocker, in anesthetized, artificially ventilated rats after unilateral vagotomy. CO(2) inhalation (maximum tracheal CO(2) concentration ranging from 9 to 12%) for approximately 60 s decreased the impulse activity of deflationary SARs but had no significant effect on tracheal pressure (P(T)) as an index of bronchomotor tone. Acetazolamide treatment (20 mg/kg) diminished the inhibitory response of deflationary SARs to CO(2) inhalation. 4-AP (0.7 and 2.0 mg/kg) dose-dependently attenuated the decrease in deflationary SAR activity induced by CO(2) inhalation. When comparing the maximum attenuation due to 4-AP (2.0 mg/kg) and acetazolamide (20 mg/kg) in CO(2)-induced deflationary SAR inhibition, blockade of K(+) channels had a more pronounced effect. These results suggest that inhibition of deflationary SARs by CO(2) inhalation may be largely mediated by the stimulating action of 4-AP-sensitive K(+) currents in the nerve terminals of the receptors.
authors.affiliation: Department of Physiology, Nippon Dental University, School of Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan. matsu-s@tky.ndu.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: T
authors.initials: T
authors.lastname: Nishikawa
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
authors.forename: J
authors.initials: J
authors.lastname: Kadoi
authors.forename: T
authors.initials: T
authors.lastname: Tanimoto
authors.forename: C
authors.initials: C
authors.lastname: Saiki
authors.forename: M
authors.initials: M
authors.lastname: Takeda
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology*; D000086:Acetazolamide / Q000494:pharmacology*; D000222:Adaptation, Physiological / Q000187:drug effects; D000280:Administration, Inhalation; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011661:Pulmonary Stretch Receptors / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015656:Respiratory Mechanics / Q000502:physiology; D013329:Structure-Activity Relationship; D014628:Vagotomy
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D026902:Potassium Channel Blockers; D002245:Carbon Dioxide; D015761:4-Aminopyridine; D000086:Acetazolamide