Title
Cellular fibronectin and von Willebrand factor concentrations in plasma of rats treated with monocrotaline pyrrole
Author
Schultze, A.E.
Emeis, J.J.
Roth, R.A.
Gaubius Instituut TNO
Publication year
1996
Abstract
The monocrotaline pyrrole (MCTP)-treated rat is a useful model for the study of certain chronic pulmonary vascular diseases. A single, i.v. administration of a low dose of MCTP causes pneumotoxicity, pulmonary vascular remodeling, sustained increases in pulmonary arterial pressure, and right ventricular hypertrophy in rats. The pulmonary vascular lesions are characterized by endothelial cell alterations, platelet and fibrin microvascular thrombosis, pulmonary edema, and thickening of the intimal and medial layers of the vessel wall. These lesions suggest that some dysfunction of the hemostatic system occurs in the lungs of rats treated with MCTP. We evaluated the concentrations of two adhesion proteins, cellular fibronectin (cFn) and von Willebrand factor (vWF), in the plasma of rats treated with MCTP. We hypothesized that changes in these factors occur along with markers of pneumotoxicity and ventricular hypertrophy and that such changes might contribute to the genesis of the vascular lesions. Enzyme-linked immunosorbent assays were used to measure cFn and vWF concentrations in the plasma of rats after MCTP treatment. Rats treated with a single, i.v. injection of 3.5 mg MCTP/kg body weight had delayed and progressive lung injury characterized at 5 days post-treatment by increases in the lung-to-body weight ratio and in lactate dehydrogenase activity and protein concentration in cell-free bronchoalveolar lavage fluid (BALF). Values for these markers were further increased at 8 days and reached a plateau thereafter. The number of nucleated cells within the BALF was increased at 8 and 14 days. Right ventricular hypertrophy, an indirect marker of pulmonary hypertension, was evident at 14 days. The cFn concentration was increased in plasma of rats at 8 and 14 days after treatment with MCTP. There was no difference between the vWF concentration in plasma of rats treated with MCTP and those treated with vehicle at any time. We conclude that an increase in plasma cFn concentration occurs prior to the onset of right ventricular hypertrophy and that this change is consistent with a role for cFn in the genesis of vascular remodeling and pulmonary hypertension in the MCTP-treated rat. The lung vascular injury and pulmonary hypertension in this model were not reflected in altered vWF concentration in the plasma.
Subject
Toxicology
cellular fibronectin
endothelial cell dysfunction
lung injury
monocrotaline pyrrole
pulmonary hypertension
vascular remodeling
ventricular hypertrophy
von Willebrand factor
fibronectin
lactate dehydrogenase
monocrotaline pyrrole
protein
von willebrand factor
animal experiment
animal model
article
blood level
blood vessel wall
controlled study
endothelium cell
enzyme linked immunosorbent assay
heart left ventricle hypertrophy
lung artery pressure
lung edema
lung injury
lung lavage
lung toxicity
male
nonhuman
priority journal
pulmonary hypertension
rat
thrombosis
Animals
Endothelium, Vascular
Fibronectins
Hypertension, Pulmonary
Lung
Male
Monocrotaline
Rats
Rats, Sprague-Dawley
Time Factors
von Willebrand Factor
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DOI
https://doi.org/10.1016/0006-2952(95)02152-3
TNO identifier
233195
ISSN
0006-2952
Source
Biochemical Pharmacology, 51 (2), 187-191
Document type
article