A histological method for studying the effects of drugs on mediator-induced airway microvascular leakage in rodents.
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 micrograms) 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-micron 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.
D000818:Animals; D001980:Bronchi / Q000098:blood supply* / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D013189:SRS-A / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014132:Trachea / Q000098:blood supply* / Q000187:drug effects
D013189:SRS-A; D012701:Serotonin; D006632:Histamine