Distribution of bronchoconstrictor responses in isolated-perfused rat lung.
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)
Munoz
N M
NM
Department of Medicine, University of Chicago, Illinois 60637.
Chang
S W
SW
Murphy
T M
TM
Stimler-Gerard
N P
NP
Blake
J
J
Mack
M
M
Irvin
C
C
Voelkel
N F
NF
Leff
A R
AR
D000109:Acetylcholine; D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006632:Histamine; D066298:In Vitro Techniques; D008168:Lung / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008407:Mast Cells / Q000473:pathology; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin
D012701:Serotonin; D006632:Histamine; D000109:Acetylcholine