Duodenal mucosal resistance to intraluminal acid in the rat: role of adaptive cytoprotection.
The duodenal mucosa is normally challenged by intermittent exposure to acid because of periodic gastric emptying. We studied the mechanisms of duodenal adaptation to acid in anesthetized rats. A polyvinyl chloride tube passing through a ligated pylorus was used for duodenal pulse instillations of 1 mL of saline or acid (100 or 400 mumols HCl) at 30-minute intervals. Duodenal lesions were blindly assessed using a combined macroscopic and histological score. Mucosal damage after exposure to saline or 100 mumols HCl was negligible in intact, vagotomized, and indomethacin-pretreated rats, whereas 400 mumols induced noticeable macroscopic and microscopic lesions. Interestingly, in intact and vagotomized rats, previous exposure to a 100-mumols HCl bolus significantly prevented mucosal damage by a subsequent 400-mumols bolus. This effect was not observed in indomethacin-pretreated rats. In these rats, however, intraduodenal instillation of exogenous 16,16-dimethyl prostaglandin E2 (16,16-dm-PGE2) prevented the damage induced by 400 mumols of HCl. A second protocol investigated the luminal release of bicarbonate and PGE2 in response to intraduodenal perfusion with 100 mumols of HCl. Duodenal bicarbonate release was stimulated by acid in all groups, whereas the release of PGE2 increased in intact and vagotomized rats but not in the indomethacin-pretreated group. In summary, these data suggest that adaptive cytoprotection plays a significant role in protecting the duodenal mucosa from acid. Vagal innervation and bicarbonate release do not appear to be as critical as cyclo-oxygenase activity for this mechanism.
Lugea
A
A
Digestive System Research Unit, Hospital General Vall d'Hebron, Autonomous University of Barcelona, Spain.
Salas
A
A
Guarner
F
F
Azpiroz
F
F
Malagelada
J R
JR
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000222:Adaptation, Physiological; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects* / Q000502:physiology; D006851:Hydrochloric Acid / Q000633:toxicity*; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001639:Bicarbonates; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2; D006851:Hydrochloric Acid; D007213:Indomethacin