Effects of acetazolamide and 4-aminoprydine on the responses of deflationary slowly adapting pulmonary stretch receptors to CO2 inhalation in the rat.
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.
Matsumoto
S
S
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
Ikeda
M
M
Nishikawa
T
T
Yoshida
S
S
Kadoi
J
J
Tanimoto
T
T
Saiki
C
C
Takeda
M
M
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
D002257:Carbonic Anhydrase Inhibitors; D026902:Potassium Channel Blockers; D002245:Carbon Dioxide; D015761:4-Aminopyridine; D000086:Acetazolamide