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Acute and chronic respiratory lesions induced by sulfur mustard in guinea pigs: Role of tachykinins

Technical Report ·
OSTI ID:7117599
We investigated in anesthetized guinea pigs the involvement of tachykinins in respiratory alterations after an airway intoxication by sulfur mustard (SM). Early lesions were evaluated after 5h. Respiratory system resistance (R) and compliance were measured by the occlusion method and airway microvascular permeability by measuring the Evans Blue dye concentration in the trachea and main bronchi. Two groups of animals were studied treated with capsaicin (which induces a tachykinin depletion) or by its vehicle. Capsaicin pretreatment had no effect on the measured parameters. We also measured 14 J after the intoxication tracheal epithelium neutral endopeptidase (NEP) (the main enzyme which degrades tachykinins). In addition bronchial responsiveness to exogenous substance P was studied in two groups of animals intoxicated with SM or not. Tracheal epithelium NEP activity was decreased from 0.448 + or 0.027 nmol.min- 1.mg protein- 1 in controls to 0. 182 + or 0.038 in intoxicated animals. Response to substance P was greater in intoxicated animals with R=2.98 + or - 1.57 cmH20.MI-1.s versus 0.35 + or 0.02 in controls, after 5.10-5 M aerosolized substance P These results suggest tachykinins are not preponderant in the early stage lesions but that bronchial hyperactivity is present at recovery, related to epithelium NEP depletion.
Research Organization:
Army Medical Research Inst. of Chemical Defense, Aberdeen Proving Ground, MD (United States)
OSTI ID:
7117599
Report Number(s):
AD-P-008765/0/XAB
Country of Publication:
United States
Language:
English

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