Effects of hemorrhagic shock on alkaline secretion and mucosal tolerance to acid in rat duodenum. A comparative study with indomethacin.
The effects of hemorrhagic shock (HE) on duodenal HCO3- secretion and mucosal tolerance to acid were investigated in anesthetized rats and compared with those of indomethacin. HE was performed by bleeding from the carotid artery to reduce arterial blood pressure to about 50 mm Hg (3 ml bleeding per 200 g of body weight) with a significant decrease in arterial pH and [HCO3-], and indomethacin was given subcutaneously in a dose of 5 mg/kg. The proximal duodenum (1.7 cm) secreted HCO3- at the rate of 1.5-1.8 mueq/15 min (3.5-4.2 mueq/cm/hr), and responded to luminal acid (10 mM HCl for 10 min) by a significant rise in HCO3- output. Indomethacin had no effect on basal HCO3- output but significantly inhibited the acid-induced HCO3- secretion, while under HE conditions duodenal HCO3- output significantly declined and failed to increase in response to luminal acidification. Subcutaneously administered 16,16-dmPGE2 (30 micrograms/kg) significantly increased HCO3- secretion in the presence of indomethacin but had less effect on the impaired HCO3- output caused by HE. In contrast, intravenous infusion of NaHCO3 (3 mmol/kg/hr) ameliorated the acid-base imbalance caused by HE, and significantly restored the impaired HCO3- responses induced by HE but not by indomethacin. Both HE and indomethacin induced extensive damage in the mucosa when the duodenal loop was perfused with 50 mM HCl for 1.5 hr, and these lesions were significantly reduced by NaHCO3 infusion and 16,16-dmPGE2, respectively. These results suggest that HE impaired duodenal HCO3- secretion and reduced the tolerance of the mucosa to acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Nobuhara
Y
Y
Tanaka
H
H
Nishiwaki
H
H
Okabe
S
S
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism*; D005744:Gastric Acid; D007213:Indomethacin / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D012771:Shock, Hemorrhagic / Q000378:metabolism*
D001639:Bicarbonates; D007213:Indomethacin