AJP - Renal Physiology, Vol 249, Issue 4 518-F523, Copyright © 1985 by American Physiological Society
Biochemical changes in the pancreas of rats with chronic renal failure
G. A. Kaysen, A. P. Majumdar, M. A. Dubick, G. D. Vesenka, G. Mar and M. C. Geokas
Chronic renal failure (CRF) was produced in female Sprague-Dawley rats by
7/8 nephrectomy. Creatinine clearance was depressed significantly (P less
than 0.005) and blood urea nitrogen (BUN) increased in CRF rats when
compared with the sham-operated (S) controls. CRF caused no apparent change
in body weight but significantly increased pancreatic weight as well as
increased DNA, RNA, and protein content. Pancreatic protein-to-DNA and
RNA-to-DNA ratios were also found to be significantly higher in CRF rats
than in the S controls. Trypsin-like activity and immunoreactive cationic
trypsinogen levels were both increased in the pancreas of CRF rats, but not
in their serum. On the other hand, protease inhibitory activity in the
pancreas and serum was significantly decreased by CRF. The ability of the
dispersed pancreatic acini isolated from CRF rats to incorporate
[3H]-leucine into protein, in the absence and presence of 0.25 nM
cholecystokinin octapeptide (CCK-8), was found to be lower than in the
controls. Furthermore, discharge of both trypsinogen and chymotrypsinogen
induced by CCK-8 was markedly reduced from acini of CRF rats as compared
with the S controls. In contrast, lactate dehydrogenase (LDH) was released
more readily from pancreatic acini of CRF. It is concluded that mild CRF
produces hyperplasia and hypertrophy of the pancreas and lowers the
responsiveness of acini to CCK-8 with respect to synthesis and secretion of
proteins.
