The chronically reserpinized rat as an animal model for cystic fibrosis: I. Acute effect of isoproterenol and pilocarpine upon pulmonary lavage fluid.

Lung lavage samples from rats treated in a chronic fashion with reserpine 
had mean increases of 133, 170, and 120% in the total 
protein, lipid, and carbohydrate contents, respectively, when compared with those of 
untreated control animals, when these values were expressed in terms of 
body weight. An acute single ip injection of the beta-adrenergic agent 
isoproterenol (10 mg) increased the glycoprotein content of pulmonary lavage fluid 
from control rats approximately 15-19%, but only 9-10% in those from 
reserpine treated rats. By contrast, pilocarpine (10 mg), administered in the 
same manner, caused a 15% increase in the total protein, carbohydrate, 
and lipid content of lavage samples from control rats and increased 
these same constituents in the lavage samples of reserpine treated rats 
98, 102, and 80%, respectively. The increased total carbohydrate content in 
the lavage samples of the treated animals was not associated with 
changes in the percent distribution of neutral sugars, amino sugars, or 
sialic acid. The ratio of these various sugar components did not 
change in the lavage samples of control or reserpine treated rats 
upon stimulation with either pilocarpine or isoproterenol. The increased total lipid 
content fround in the lavage samples from the treated rats probably 
results from an increase in phospholipids. A decrease in phospholipid content 
occurred in the lavage samples of reserpine treated rats upon stimulation, 
while the opposite was observed in those of control animals. Chronic 
treatment of rats with reserpine, thus, appears to induce an enhanced 
production of glycoproteins in the airways and to interfere with phospholipid 
metabolism in the lung. In addition, the drug treatment enhances the 
secretory response to pilocarpine in comparison with the responses of control 
animals. The enhanced response or hypersecretion of glycoproteins is a quantitative 
one and does not seem to involve alterations in the ratios 
or distribution of the various sugar components. This disturbance in the 
secretory function of the respiratory tract, a target organ which is 
prominently involved in cystic fibrosis (CF) together with alterations in other 
exocrine glands which resemble those of CF patients, makes the reserpine 
treated rat a useful model for further study of possible pathogenetic 
mechanisms in CF. The experimental animal model for CF developed by 
the chronic administration of reserpine to rats has been found to 
have changes in the protein content of lung lavage samples, in 
addition to morphologic and secretory alterations in the salivary glands and 
the pancreas. Further analysis of the organic composition of lung lavage 
samples shows that the protein, carbohydrate, and lipid contents are significantly 
increased after chronic reserpine administration and that the response to stimulation 
with pilocarpine is enhanced in the treated animals when compared to 
that of untreated control rats. It therefore appears that chronic reserpine 
administration causes a hypersecretion of glycoproteins and changes in lipid metabolism 
in the respiratory tract of the rat and that, in conjunction 
with previous findings in other exocrine glands, these effects on lung 
function make the reserpine treated rat a useful tool for the 
study of the pathologic disturbance seen in the major exocrine glands 
affected in CF. 