Hypoxia/reoxygenation impairs glucose absorption and cAMP-mediated secretion more profoundly than glutamine absorption and Ca2+/PKC-mediated secretion in rat ileum in vitro.

BACKGROUND

Intestinal ischemia and reperfusion may lead to profuse secretion of water and electrolytes. The underlying mechanisms have been related to increased hydrostatic pressure, to denudation of intestinal villi, and, recently, to adenosine-mediated enhancement of chloride secretion.

METHODS

We studied the effects of hypoxia and reoxygenation on baseline electrophysiologic parameters; on glucose- and glutamine-induced absorption; on secretion induced by carbachol, histamine, and forskolin; and on epithelial barrier function to disodium-fluorescein and horseradish peroxidase in rat ileum mounted in Ussing chambers.

RESULTS

We observed that 30 minutes of hypoxia followed by 60 minutes of reoxygenation differentially affected glucose and glutamine absorption to 11% and 42%, respectively, of control values. Cyclic adenosine monophosphate-mediated secretion induced by forskolin was reduced to 9% of controls. In contrast, Ca(2+)/protein kinase C-mediated secretion induced by carbachol or histamine was reduced only to 35% to 48% of controls. Furthermore, the epithelium fully was capable of maintaining its barrier function to small and large permeability probes, even after 90 minutes of hypoxia.

CONCLUSIONS

We conclude that hypoxia and reoxygenation differentially impair nutrient absorption, corroborating recent absorption data in in vivo models of ischemia, and that it differentially affects secretory capacity in crypts, dependent on the intracellular messenger pathway. The relative persistence of Ca(2+)/protein kinase C-mediated secretion to hypoxia and reoxygenation indicates that secretagogues that activate this pathway play a significant role in the intraluminal fluid sequestration and diarrhea observed after intestinal ischemia and reperfusion.