Lung lavage samples from rats treated with reserpine had mean increases of 133, 170 and 120% in the total protein, lipid and carbohydrate contents, respectively, compared with untreated control animals when the values were expressed in terms of body weight. An acute single i.p. injection of the .beta.-adrenergic agent isoproterenol (10 mg) increased the glycoprotein content of pulmonary lavage fluid from control rats .apprx. 15-19% but only 9-10% in those from reserpine treated rats. Pilocarpine (10 mg) given i.p. caused a 15% increase in the total protein, carbohydrate and lipid content of lavage samples from control rats and increased the 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 the 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 found in the lavage samples from the treated rats is probably are from an increase in phospholipids. A decrease in phospholipid content occurred in the lavage samples of reserpine treated rats upon stimulation, the opposite was seen in control animals. Chronic treatment of rats with reserpine appears to induce production of glycoproteins in the airways and to interfere with phospholipid metabolism in the lung. 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 and does not not seem to involve changes in the ratios or distribution of the various sugar components. This disturbance in the secretory function of the respiratory tract, a target organ prominently involved in cystic fibrosis (CF) together with changes in other exocrine glands which resemble those of CF patients, makes the reserpine treated rat a useful model for the study of possible pathogenetic mechanisms in CF. The experimental animal model for CF developed by the chronic administration of reserpine to rats has changes in the protein content of lung lavage samples and to morphologic and secretory changes in the salivary glands and the pancreas. 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 the response to stimulation with pilocarpine is enhanced in the treated animals when compared to that of untreated control rats. Apparently, chronic reserpine administration causes a hypersecretion of glycoproteins and changes in lipid metabolism in the respiratory tract of the rat and in conjunction with previous findings in other exocrine glands, the effects on lung function make the reserpine treated rat useful for the study of the pathologic disturbance seen in the major exocrine glands affected in CF.
