Impairment of acid-neutralizing capacity and lesion formation in the rat duodenum during hemorrhagic shock: comparative study with indomethacin.
The effects of hemorrhagic shock (HE) on duodenal pH, acid-neutralizing capacity and mucosal tolerance to acid were investigated in anesthetized rats, and they were compared with those of indomethacin. HE was performed by bleeding from the carotid artery to reduce arterial blood pressure to about 55 mmHg (3 ml of bleeding per 200 g of body weight), and indomethacin was given s.c. in a dose of 5 mg/kg. Duodenal pH was determined in the outflow from the proximal duodenum (1.7 cm) which was perfused with 10(-4) M HCl, and acid-neutralizing capacity was measured by back-titration of the perfusate to pH 4.0 with 10 mM HCl. Under these conditions, duodenal pH was kept at around 6.0 as the result of neutralization in the loop (approximately 8 microEq/hr). Both HE and indomethacin significantly decreased the pH and acid-neutralizing capacity. Administration of 16,16-dimethyl prostaglandin E2 (16-dmPGE2: 30 micrograms/kg, s.c.) significantly increased both pH and acid-neutralizing capacity in normal and indomethacin-treated rats, but failed to affect these parameters in rats under HE conditions. When the duodenal loop was perfused with 50 mM HCl for 1.5 hr, both HE and indomethacin induced extensive damage in the mucosa. Pretreatment with 16-dmPGE2 significantly reduced the formation of duodenal lesions induced by indomethacin but not by HE. These results suggest that HE as well as indomethacin impaired duodenal acid-neutralizing capacity to reduce the tolerance to acid of the mucosa. The deleterious effects of HE on the mucosa may be mainly due to a decreased mucosal blood flow, but not due to a deficiency of endogenous prostaglandins.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Furukawa
O
O
Tanaka
H
H
Nishiwaki
H
H
Okabe
S
S
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D004386:Duodenum / Q000187:drug effects; D006851:Hydrochloric Acid / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012771:Shock, Hemorrhagic / Q000503:physiopathology*
D011459:Prostaglandins E, Synthetic; C017244:16,16-dimethylprostaglandin E; D006851:Hydrochloric Acid; D007213:Indomethacin