The incidence of duodenal ulcer increases with age, but acid secretion does not. We have investigated the effects of aging on a mechanism of duodenal mucosal defense. Basal and acid-stimulated bicarbonate secretions were measured in the proximal duodenum in anesthetized rats of three different age groups (3 months, 1 year, and 2 years). The proximal duodenum was cannulated in situ between two plastic tubes that extend downward from a titrating chamber, and bicarbonate secretion was measured by the method of Flemström et al. Although there was no significant difference in basal secretion among three groups, bicarbonate secretion in response to luminal acid (100 mmol/L [millimolar] HCl) was diminished in 1-year-old and 2-year-old rats (1-hour integrated bicarbonate secretions; 3 months = 5.8 +/- 0.7; 1 year = 3.1 +/- 1.0*; 2 years = 2.0 +/- 0.7*). We also studied the effects of two mediators for acid-stimulated duodenal bicarbonate secretion, vasoactive intestinal polypeptide (VIP), and prostaglandin E2 (PGE2). Intravenous infusion of VIP (0.4, 4, 40 nmol/kg/hr) and intraluminal administration of PGE2 (10(-5) mol/L [molar] and 10(-4) mol/L) induced duodenal bicarbonate secretion in a dose-dependent manner in all three groups, without significant difference between groups. These findings suggest that the release of mediator(s) in response to acid is decreased in the duodenum of the aging rats. The progressive breakdown in mucosal defense mechanisms with increasing age may explain, at least in part, the age-related increase of incidence of duodenal ulcer disease.