Alterations in jejunal transport and (Na+-K+)-ATPase in an experimental model of hypoxia in rats.
Hypoxia was induced by exposing rats to an atmosphere of 93% N2, 7% O2 for 4-48 hr. The animals became hypoxic as indicated by a decreased blood PaO2 (mean +/- SEM: 48 +/- 10 mm Hg). Hypoxia was accompanied by metabolic acidosis (pH 7.22 +/- 0.02) and decreased serum bicarbonate levels (9.0 +/- 4.0 meq/liter). Hypoxic rats also showed evidence of tissue hypoxia; liver tryptophan oxygenase levels were increased to 21 +/- 2 nmole/min/mg protein. In the hypoxic animals there was decreased jejunal mucosal (Na+-K+)-ATPase activity and an inhibition of active intestinal transport of sodium, glucose, 3-O-methylglucose, galactose, tyrosine, phenylalanine, and glycine as determined by in vivo perfusion studies. Jejunal fructose transport, which has a large passive component, was unaffected by hypoxia. The electrolyte, carbohydrate, and amino acid transport alterations produced by hypoxia were seen in the absence of an effect on jejunal cell number, DNA synthesis, or cell turnover. There was also no evidence of histological or ultrastructural damage. Furthermore, studies with a luminal macromolecular tracer, horseradish peroxidase, indicated that the jejunal lumen-to-blood barrier to macromolecules was also unaltered in these hypoxic animals. In vitro local oxygenation of the jejunum, by bubbling of 95% O2:5% CO2, markedly improved sodium and glucose (but not 3-O-methylglucose) absorption in hypoxic rats and control rats. The (Na+-K+)-ATPase activity of the jejunal mucosa of hypoxic rats was significantly enhanced by the local bubbling of 95% O2:5% CO2. Overall, our data indicate that during relatively mild conditions of hypoxia there is an inhibition of jejunal (Na+-K+)-ATPase activity and related transport processes that is prevented by in situ oxygenation.
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D050260:Carbohydrate Metabolism; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000201:enzymology; D007583:Jejunum / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D010100:Oxygen / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis*
D000596:Amino Acids; D004247:DNA; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D010100:Oxygen