A histological method for studying the effects of drugs on mediator-induced airway microvascular leakage in rodents

O'Donnell S.R., Braun R.A., Reid J.J. and Wholohan T. (1987) A histological method for studying the effects of drugs on mediator-induced airway microvascular leakage in rodents. Journal of Pharmacological Methods, 17 3: 205-217. doi:10.1016/0160-5402(87)90051-9


Author O'Donnell S.R.
Braun R.A.
Reid J.J.
Wholohan T.
Title A histological method for studying the effects of drugs on mediator-induced airway microvascular leakage in rodents
Journal name Journal of Pharmacological Methods   Check publisher's open access policy
ISSN 0160-5402
Publication date 1987-01-01
Sub-type Article (original research)
DOI 10.1016/0160-5402(87)90051-9
Open Access Status Not Open Access
Volume 17
Issue 3
Start page 205
End page 217
Total pages 13
Subject 3004 Pharmacology
Abstract Methods are described for studying the effects of drugs on increases in tracheobronchial microvascular permeability (leakage) induced by inflammatory mediators. A model in conscious guinea pigs (in which the leakage effects resulted from circulating mediator) and a model in anesthetized rats (in which the leakage effects resulted from application of the mediator to the airway lumen) are described. Inhibitor drugs were given i.v. 2 min before the mediator. In guinea pigs either histamine or leukotriene D4 (LTD4) and colloidal carbon (C, the tracer molecule for leakage) were administered together iv.; in rats 5-hydroxytryptamine (5-HT, 100 μg) was injected intratracheally followed by i.v. colloidal carbon. Tracheal and bronchial tissues were removed 15 min later from the killed animals and prepared for histology, and the number of C-labeled microvessels in the mucosal/submucosal region of 7-μm sections was counted. In guinea pigs, leakage produced by LTD4 or histamine was related to the dose administered and the relative potency of LTD4: histamine was approximately 123:1, on a molar basis. Leakage caused by histamine, but not by LTD4, was prevented by mepyramine (1 mg/kg) and LTD4-induced leakage was prevented by FPL 55712 (1 mg/kg). Terbutaline (1 mg/kg) attenuated leakage to both mediators but never abolished it. In rats, leakage was also seen to 5-HT, which was prevented by methysergide (1 mg/kg) and markedly attenuated by ketanserin (1 mg/kg) or by terbutaline (1 mg/kg). It is suggested that the colloidal carbon tracer technique has application to pharmacological studies designed to examine the effects of drugs on mediator-induced permeability to macromolecules in the tracheobronchial microcirculation.
Keyword 5-Hydroxytryptamine
Carbon-labeled microvessels
Histamine
Leukotriene D4
Microvascular permeability
Trachea and bronchi
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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