The Chronically Reserpinized Rat as a Possible Model for Cystic Fibrosis. II. Composition and Cilioinhibitory Effects of Submaxillary Saliva

Abstract

Extract: Submaxillary saliva was obtained from rats treated for 7 days with a daily dose of 0.5 mg/kg reserpine and from untreated controls. Secretory (volume) response, total protein, total carbohydrate, and Na⁺ and Ca⁺⁺ concentrations were compared. After pilocarpine stimulation, saliva from treated animals showed significantly elevated concentrations of Na⁺, Ca⁺⁺, total protein, and total carbohydrate. Total volume output was only 20% and maximum flow rate was 50% of those in control animals. A single injection of guanethidine (2 mg/kg) 30 min before stimulation increased the volume output and resulted in normal protein concentrations in saliva from reserpinized animals. Treatment of the animals with isoproterenol (5 mg/kg daily) for 7 days after three doses of reserpine also partially restored the volume response to pilocarpine, but resulted in higher protein outputs. The reverse treatment (isoproterenol followed by reserpine) did not change the volume output but resulted in even higher ratios of secreted protein per unit of gland weight. Stimulation of salivary secretion with isoproterenol resulted in very high protein concentrations and in a markedly increased total protein output in reserpinized animals. Both pilocarpine and isoprote-renol-stimulated saliva from reserpinized rats showed ciliostatic effects when added to gills of fresh water mussels. Such effects were similar to those produced by serum from patients with cystic fibrosis.

Since a decreased secretory response and elevated concentrations of Na⁺, Ca⁺⁺, protein, and carbohydrate have been found in submaxillary saliva of cystic fibrosis (CF) patients, the results obtained in these experiments suggest that the reserpinized rat may provide a potential animal model for studying the pathogenesis of the disease. This view is further supported by the demonstration of cilioinhibitory properties in the saliva of treated animals, which are similar to those of CF serum.

Speculation: Treatment of rats with reserpine for 7 days results in elevations of Na⁺, Ca⁺⁺, protein, and carbohydrate concentrations in submaxillary saliva secreted after a pilocarpine stimulus. These findings are similar to those reported in submaxillary saliva from CF patients after parasympathomimetic stimulation and suggest a possible model for the study of the secretory abnormality in the disease. The demonstration of ciliotoxic properties in saliva from the treated animals, which closely resemble those of CF serum, lends support to the concept of an animal model.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD