Journal of Applied Physiology, Vol 66, Issue 1 202-209, Copyright © 1989 by American Physiological Society
Distribution of bronchoconstrictor responses in isolated-perfused rat lung
N. M. Munoz, S. W. Chang, T. M. Murphy, N. P. Stimler-Gerard, J. Blake, M. Mack, C. Irvin, N. F. Voelkel and A. R. Leff
Department of Medicine, University of Chicago, Illinois 60637.
We studied the effects of bronchoconstrictor stimuli administered
selectively through isolated-perfused preparations of the bronchial and
pulmonary circulations of 80 Sprague-Dawley rats. Dose-related contraction
was elicited with infusion of acetylcholine (ACh), histamine, and serotonin
(5-HT). Bolus infusion of 10(-5) mol ACh caused a 3.5-fold increase in
pulmonary resistance (RL) after infusion into the pulmonary circulation
(PC) and a 2.5-fold increase in the bronchial circulation (BC) (P less than
0.05 vs. control) that was blocked selectively in each circulation with
atropine. Administration of 10(-5) mol 5-HT into the BC caused only a 45%
increase in RL; the same dose of 5-HT caused a 5.1-fold increase in RL in
the PC. A biphasic (increase at lower doses/decrease at higher doses)
change in RL was elicited by histamine that was converted to dose-related
constriction after H2-receptor blockade with cimetidine in both BC and PC.
Response to exogenous ACh remained viable for greater than 5 h. Infusion of
the mast cell degranulating agent, compound 48/80 (48/80), caused increase
in RL that corresponded to quantitative recovery of histamine in the
perfusates of both BC and PC. Histamine concentration in the perfusate
increased from 47.2 +/- 31.8 (base line) to 624 +/- 60.1 ng/ml (2-fold
increase in RL) in the BC and from 38.3 +/- 17.7 (base line) to 294.4 +/-
38.1 ng/ml (50% increase in RL) in the PC (P less than 0.001 vs. baseline
concentration) after a 0.1-mg/ml dose of 48/80.(ABSTRACT TRUNCATED AT 250
WORDS)
