ABSTRAm. The chronically reserpine-treated rat, an experimental model for cystic fibrosis, exhibits generalized exocrinopathy, impaired pancreatic secretion, and decreased pancreatic amylase. Although chronic reserpine treatment induces malnutrition by decreasing food consumption and growth, the effects of this malnutrition per se on the exocrine pancreas have not been considered. In this study, the effects of chronic reserpine treatment and malnutrition on the exocrine pancreas were determined using pair-fed controls. Male, Sprague-Dawley rats were treated daily subcutaneously for 5 to 7 days with: I ) no injection (control), 2) 1.0 mllkg vehicle or sham (controlsham, pair fed-sham), or 3) 0.5 mglkg reserpine (chronically reserpine-treated). Both chronic reserpine-treatment and pair-feeding significantly decreased food consumption (40%), body weight (51 and 59%), total pancreatic amylase (49 and 56%) and specific amylase activity (62 and 61%), pancreatic protein (65 and 75%), and pancreatic weights (62 and 65%) compared to controls. These decreases, however, were comparable between the chronically reserpine-treated and pair fed-sham rats. In contrast, the secretory response to the biologicalls active cholecvstokinin analog cho~ec~stokinin octaieptidk was significantly attenuated in isolated oancreatic acini oreoared from reser~ine-
ABSTRACT. Chronic reserpine treatment (500 pg/kg) of the rat results in generalized exocrinopathy, impaired pancreatic secretion, and decreased pancreatic amylase. These characteristics are similar to those in cystic fibrosis and are the basis for use of this experimental model for cystic fibrosis. Pancreatic enzymes adapt to diet, but it is not known whether chronic reserpine treatment affects this response. Due to the malnutrition induced by this treatment, another dose of reserpine was required that would alter pancreatic function but not induce malnutrition in order to evaluate dietary adaptation. Male rats (100-120 g) were injected subcutaneously daily for 7 days with 1) no injection (control); 2) 1.0 ml/kg vehicle or sham (pair fedsham); or 3) reserpine: 500,50, or 5 pglkg. Food consumption was comparable among control and reserpine-treated (50 and 5 pg/kg) rats and significantly greater (200%) than pair fed-sham and 500 pg/kg reserpine-treated rats. Pancreatic amylase, however, was significantly lower in all reserpine-treated rats (500 pg/kg, 74%; 50 pg/kg, 56%; 5 pglkg, 52%) than in control rats. To evaluate dietary adaptation, control and reserpine-treated (5 pg/kg) rats were fed high carbohydrate, high fat or high protein diets. Both groups adapted to these diets with the greatest amylase, lipase, and trypsin activities in high carbohydrate-, high fat-, and high protein-fed rats, respectively. Reserpine-treated rats fed high carbohydrate, however, had significantly lower (64%) amylase activity than high carbohydrate-fed control rats. Although reserpine-treated rats can adapt pancreatic enzymes to diet, the adaptation of amylase to carbohydrate is impaired. (Pediatr Res 23: 176-180,1988) Abbreviations PFS, pair-fed sham C, control R500, reserpine-treated with 500 pglkg R50, reserpine-treated with 50 pg/kg R5, reserpine-treated with 5 pg/kg HC, high carbohydrate HF, high fat HP, high protein ANOVA, analysis of variance LSD, least significant difference
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