Journal of Applied Physiology, Vol 73, Issue 6 2343-2348, Copyright © 1992 by American Physiological Society
Systemic pilocarpine increases deposition of and decreases responsiveness to inhaled carbachol in sheep
L. Garcia, C. S. Kim, R. Forteza and A. Wanner
Pulmonary Division, University of Miami School of Medicine, Mount Sinai Medical Center, Florida 33140.
The purpose of this study was to determine whether excessive airway
secretions could serve as a barrier function against inhaled particulate
matter. To increase airway secretions, six conscious sheep were treated
with pilocarpine (0.8 mg/kg i.v.). Pilocarpine increased pulmonary
resistance (RL) and total aerosol deposition within five breaths (AD5) as
determined by the rebreathing of an inert monodisperse aerosol. When RL had
returned to baseline, AD5 remained elevated [21 +/- 2% (SE), P < 0.05]
and tracheal secretions were increased (237 +/- 77%, P < 0.05) above the
values before pilocarpine administration. A carbachol aerosol dose-response
curve was carried out at this time and compared with a control carbachol
dose-response curve by calculating the dose of carbachol required to
increase RL by 400% (PD400). Mean PD400 was increased postpilocarpine by 53
+/- 18 (P < 0.05) and 85 +/- 25% (P < 0.05) when normalized for
increased aerosol deposition. Thus, pilocarpine decreased airway
responsiveness to inhaled carbachol despite increasing aerosol deposition.
The pilocarpine-induced airway hyporesponsiveness to inhaled carbachol is
consistent with the hypothesis that excessive secretions have a protective
role in the airways.
