Distribution of bronchoconstrictor responses in isolated-perfused rat lung

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Abstract
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 < 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 < 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 < 0.001 vs. baseline concentration) after a 0.1-mg/ml dose of 48/80. We demonstrate a method that permits selective assessment of mast cell secretion and pharmacological response to contractile agonists in central and peripheral compartments of the lung. Substantial differences in physiological and mast cell secretory responses are demonstrated between these regions.