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Altered Capillary Filtration Coefficient in Parathion- and Paraoxon-Induced Edema in Isolated and Perfused Rabbit Lungs
Delaunois, Annie; Gustin, Pascal; Ansay, Michel
1992In Toxicology and Applied Pharmacology, 116 (2), p. 161-169
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Keywords :
Edema; Rabbit; Lungs
Abstract :
[en] Changes in pulmonary endothelium permeability and in microvascular hemodynamics induced by parathion (Pth) and paraoxon (Pox), its active metabolite, were investigated in isolated, perfused rabbit lungs. Blood-free perfusate was recirculated through isolated and ventilated lungs in an isogravimetric state and in zone III conditions. The arterial/venous/double occlusion technique was used to divide the total vascular resistance (Rt) into four components: arterial, precapillary, postcapillary, and venous. The capillary filtration coefficient (Kfc) was evaluated by measuring the amount of fluid filtering through the endothelium when the arterial and venous pressures were suddenly increased. Pth and Pox induced pulmonary edema by increasing endothelium permeability without changing the hemodynamic parameters at any level of the vascular bed. The Kfc value increased progressively, reaching a maximum (Emax) 60 min after administration of organophosphate (558 ± 65% (n = 5) and 707 ± 109% (n = 5) of baseline values, for Pth and Pox, respectively). During the next 60 min, it decreased. The time course of Pox-induced changes in Kfc was similar to that obtained with Pth. The concentration-response curve (Emax) expressed as a percentage of the baseline value versus the logarithm of the malor Pth concentration, ranging from 2 × 10−5 to 4 × 10−4 image) was linear (y = 1661.1 + 327.3x, R = 0.89, p < 0.001, N = 14). Piperonyl butoxide (4 × 10−4 image), an inhibitor of cytochrome P450, had a strong protective effect against Pth (4 × 10−4 image)-induced alterations of endothelium permeability (n = 5, p < 0.001). The effects of Pox (4 × 10−4 image) on Kfc were completely abolished by pretreatment with 10−5 image atropine, as shown by the significantly lower Emax value recorded in atropine-pretreated lungs (129 ± 33%, n = 4) than in Pox-treated lungs (707 ± 109%, n = 5, p < 0.001). The effects of Pth, on the other hand, were only partially inhibited, since the Emax value recorded in atropine-pretreated lungs (196 ± 20%, n = 4) remained significantly higher than that recorded for control lungs (129 ± 15%; n = 5; p < 0.05). These results show that isolated and perfused rabbit lungs constitute and appropriate model for studying the direct pulmonary effects of organophosphates. The edema-inducing action of Pth depends on its activation by conversion to Pox in the lung tissue. It can be explained by an increase in endothelium permeability. This effect is mediated principally by muscarinic receptors
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Delaunois, Annie ;  Université de Liège - ULiège
Gustin, Pascal ;  Université de Liège - ULiège > Département de sciences fonctionnelles > Pharmacologie, pharmacothérapie et toxicologie
Ansay, Michel ;  Université de Liège - ULiège
Language :
English
Title :
Altered Capillary Filtration Coefficient in Parathion- and Paraoxon-Induced Edema in Isolated and Perfused Rabbit Lungs
Publication date :
1992
Journal title :
Toxicology and Applied Pharmacology
ISSN :
0041-008X
eISSN :
1096-0333
Publisher :
Academic Press, New York, United States - New York
Volume :
116
Issue :
2
Pages :
161-169
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 25 August 2009

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