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To assess the effects of hypothyroidism (HT) on small-intestinal function, HT was induced in rats (120-150 g) by methimazole in drinking water. After 6 wk of methimazole, intestinal absorption studies were performed in HT and in control (C) rats by in situ luminal perfusion of a 20-cm proximal jejunal loop with a bicarbonate buffer containing sodium, glucose or fructose, glycine or lysine, and phenol red as a nonabsorbable marker for determination of water fluxes. Mucosa from the perfused segment was taken for assay of disaccharidases and ATPases and for light and electron microscopy. Compared with C rats, HT rats had significantly lower jejunal transport rates of water (2.54 +/- 0.36 versus 5.02 +/- 0.7 microL/min/microgram mucosal protein, p < 0.03), sodium (37.1 +/- 10.3 versus 102.7 +/- 18.6 mumol/min/microgram protein, p < 0.05), and glucose (1.49 +/- 0.28 versus 5.17 +/- 0.82 mumol/min/microgram protein, p < 0.02). A reduction in glycine transport was also observed but did not attain statistical significance (p = 0.058). Fructose and lysine transport was unchanged. Mucosal sucrase and lactase activities were similar in both groups, but Na,K-ATPase was significantly lower in HT rats (1.17 +/- 0.3 versus 4.03 +/- 1.5 mumol inorganic phosphate/h/mg protein; p < 0.05), with a diminution of ouabain binding sites by 41.5%. Light microscopy of jejunal mucosa from HT rats did not differ from that from C rats; electron microscopy showed mild mitochondrial swelling in HT enterocytes. A group of HT rats were treated with L-thyroxine during 4 wk; these rats had absorption rates, mucosal enzyme activities, ouabain binding, and mucosal morphology not different from C rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The assumption that fresh cow's milk may have a direct effect on jejunal mucosal macromolecular permeability was tested in 14-day-old suckling guinea pigs, by in situ luminal perfusion of a proximal jejunal segment with horseradish peroxidase administered either in 0.9% NaCl or in cow's milk. For positive control, a group of guinea pigs previously sensitized to beta-lactoglobulin was similarly perfused with horseradish peroxidase in 0.9% NaCl or in cow's milk at 14 days of age. A segment of the wall of the perfused jejunal loop was processed for peroxidase staining and for examination of the extent and routes of macromolecular absorption by light and electron microscopy. Mucosal exposure to cow's milk was associated with penetration of tracer material across the jejunal epithelium only in the lactoglobulin-sensitized guinea pigs. In guinea pigs with a first-time exposure to cow's milk, no entry of tracer material beyond the brush border surface of the enterocytes was seen. Thus, whereas we could observe absorption of bystander antigens during antigenic challenge of the mucosa in sensitized animals, we found no evidence of a presumptive "permeability factor" in cow's milk that can disrupt the mucosal macromolecular barrier by an acute direct action.

We studied the effects of increased circulating levels of bile salts on jejunal mucosal function in dogs. In situ luminal perfusion of a 30-cm proximal jejunal segment was performed while deoxycholate, cholate, taurodeoxycholate, or taurocholate solutions were directly added to the mesenteric arterial supply, reaching the intestinal wall at successive concentrations of 5, 8, 12, and 22 mumol/L. The transport rates of water, sodium, glucose, fructose, glycine, and lysine were measured. The mucosa of the experimental loop was assayed for ATPase activity, and examined by light and electron microscopy. Deoxycholate at 8 microM in the blood supply of the perfused jejunal segment was associated with a significant (p less than 0.02) reduction in the absorption rates of water, sodium, glucose, and glycine, and inhibition of mucosal Na+, K+-ATPase. The absorption of fructose and lysine, and brush border enzyme activities, were not affected. Cholate had a similar effect at 12 microM. There were no obvious histological alterations, but electron microscopy showed swelling of mitochondria in the enterocytes. The reduction in mucosal transport, the inhibition of mucosal Na+, K+-ATPase, and the mitochondrial swelling were reversed after discontinuation of the bile salt infusion. The taurine conjugates at 22 microM depressed transport of water and sodium only, and did not inhibit Na+, K+-ATPase. Our study indicates that increased circulating concentrations of unconjugated bile salts, particularly deoxycholate, may impair Na+, K+-ATPase-related jejunal mucosal function.

A model of nonischemic hypoxia of the jejunum was designed in dogs, by shunting of blood from the inferior vena cava directly into the regional mesenteric arterial supply, thereby lowering the PaO2 of the blood that reached the jejunal wall from 98.6 +/- 3 to 62 +/- 5 mm Hg. Absorption rates of sodium, glucose, fructose, glycine, and the dibasic aminoacid lysine were studied by in situ luminal perfusion of a 30-cm proximal jejunal segment with a bicarbonate buffer solution containing phenol red as a nonabsorbable marker for determination of water fluxes. During periods of control, hypoxia, and after discontinuation of the venoarterial admixture (recovery), effluent perfusate was collected and mucosal biopsies were obtained for assay of lactase, maltase and sucrase activity, mucosal ATPase activity and ATP content, and for light- and electron microscopic examination. Mesenteric supply with hypoxic blood was associated with a significant inhibition of Na+,K+-ATPase activity (p less than 0.001) and a rise in mucosal ATP content (p less than 0.05). There was a significant reduction in the absorption rates of sodium (p less than 0.001), glucose, and glycine (p less than 0.01), but no change in the transport of fructose and of lysine. Brush border enzymes were unaltered. The histological appearance of the mucosa remained normal throughout the experiment, but on electron microscopy a distinct swelling of the enterocyte mitochondria was noted during the hypoxia period.(ABSTRACT TRUNCATED AT 250 WORDS)