Pathogenesis of duodenal ulcer in the rat: dissociation of acid load and blood flow.
Duodenal mucosal blood flow (DMBF) and duodenal acid load were studied in nonanesthetized rats. Four groups of animals were injected with an ulcerogenic dose of mepirizole [1-(4-methoxy-6-methyl-2-pyrimidinyl)-3-methyl-5-methoxypyrazole] and were studied at 3, 6, 12, and 24 h after drug administration. Three additional groups were given an injection of the vehicle used to solubilize the drug and were studied 3, 12, and 24 h later. All animals studied 24 h after mepirizole showed ulceration of the proximal duodenum. DMBF in animals that received vehicle averaged 141 +/- 12 ml.100 g-1.min-1. A significant duodenal hyperemia was observed 3 and 6 h after mepirizole (498 +/- 113 and 377 +/- 92 ml.100 g-1.min-1, respectively). A large increase in duodenal acid load was also found at these times (47.6 +/- 2.6 and 46.4 +/- 7.3 mueq/h, respectively). DMBF declined progressively afterwards to reach subnormal levels at 24 h after mepirizole. Acid load, however, remained at a high level throughout the 24 h of observation. In contrast, no significant changes in blood flow were observed in pancreas, jejunum, ileum, or colon. In animals with a duodenal ligature 5 mm distal to the pylorus, a hyperemia was observed in the portion of duodenum in continuity with the stomach. This phenomenon was absent in the duodenum distal to the ligature. It is concluded that the high duodenal acid load observed in the face of decreasing DMBF could explain the occurrence of duodenal damage between 12 and 24 h after mepirizole administration.
Scremin
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OU
Veterans Administration Medical Center, Albuquerque, New Mexico 87108.
Leung
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FW
Guth
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PH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000503:physiopathology*; D004386:Duodenum / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*; D004840:Epirizole / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects
D004840:Epirizole