Summary .isoproterenol (8). In the second model, we have demonstratedThe chronically reserpinized rat has been proposed as an animal model for cystic fibrosis on the basis of morphologic and secretory alterations in the submaxillary gland and of abnormalities in pulmonary secretions. In this investigation, the volume and composition of pancreatic juice from reserpine treated rats (0.5 mg/kg/day) have been compared to those of untreated controls after stimulation with purified cholecystokinin (0.1 pg/ kg body wt) and with crude and purified preparations of secretin (6p/100 g body wt) infused iv for 30-min periods. The results demonstrate that the treated animals secreted a significantly lower volume of pancreatic juice after stimulation with these secretagogues. Fldw rates were also significantly reduced after stimulation with cholecvstokinin and crude secretin. Protein and amylase outputs in response to cholecystokinin were smaller than in control animals after unrestricted feedings, but greater after a 24-hr fast. Total bicarbonate output was also reduced after stimulation with either crude or purified secretin and the normal excretion patterns for bicarbonate and chloride were either absent or reversed in the secretin-stimulated pancreatic juice of the treated animals. Whole pancreas homogenates from the treated animals showed significant increases in Ca++ and protein content. These results indicate that chronic administration of reserpine alters the secretion of water, protein, and bicarbonate from the rat pancreas and that it affects several of the exocrine glands involved in cystic fibrosis. These findings lend support to the concept of an animal model for the human disease.
SpeculationThe chronic administration of reserpine to rats has been shown to induce alterations in salivary and pulmonary secretions which resemble those seen in patients with cystic fibrosis. The concept of an animal model has been proposed on the basis of these observations. The pancreas is another exocrine gland prominently involved in cystic fibrosis and if it can be demonstrated that reserpine administration also induces alterations in pancreatic secretion, the concept of the animal model would be strengthened considerably.The generalized exocrine gland dysfunction which is characteristic of cystic fibrosis (3) has been partially reproduced in experimental animal models induced by treating rats in a chronic fashion with certain drugs that influence the level of autonomic input into these tissues. In the first of these models, changes in the excretion of monovalent ions and of basic proteins from the rat parotid gland were observed after chronic administration of that administration of reserpine for several days induces morphologic and secretory changes in the rat submaxillary gland which resemble those of cystic fibrosis (CF) (11,12). In addition, we have shown that this procedure increases the secretion of total protein and of a specific type of glycoprotein from the lungs of the treated animals, in a manner that parallels the abn...