GASTRIN MEDIATES THE INCREASE IN GASTRIC CELL-GROWTH IN UREMIC RATS

In a rat model of chronic renal failure, we recently reported that hyp ergastrinemia was associated with increased stomach weight and parieta l cell and enterochromaffin-like (ECL) cell density. In this study, th e role of gastrin in mediating trophic effects of uremia on the gastri c mucosa was examined by chronic immunoneutralization of endogenous ga strin in the sub-total nephrectomy uremic rat model. Three weeks after surgery, the rats were uremic (azotemic and hypertensive). Uremic rat s had a significant increase in corpus mucosal height (17%), parietal cell density (14%), ECL cell density (27%), and basal gastric mucosal blood flow (63%). These effects were specifically inhibited by chronic administration of gastrin-specific monoclonal antibody (5 mg ip every other day) in the 3-wk postoperative period. Uremic rats also had an increase in stomach weight (23%), corpus mucosal area (8%), arterial b lood pressure, and serum creatinine and a decrease in body weight. Gas trin immunoneutralization did not alter these effects. The findings su ggest that elevated levels of endogenous circulating gastrin in uremic rats mediate, in part, the trophic response observed in the gastric m ucosa.