Mucosal dysfunction in the cat small intestine.
Kubes, Paul, Paul H. Reinhardt, Derrice Payne, and Richard C. Woodman.
Departments of Medical Physiology and Medicine, University of
Calgary Medical Center, Calgary, Alberta, T2N 4N1
APStracts 2:0038G, 1995.
The overproduction of nitric oxide in the small bowel has been invoked
as a cytotoxic event in the vascular, mucosal and whole organ
dysfunction associated with inflammation. We assessed whether
exogenous administration of nitric oxide in the form of nitric oxide
donors (CAS 754, SIN-1) could cause microvascular and mucosal barrier
dysfunction in vivo, or epithelial and endothelial cell permeability
alterations and cell injury in vitro. Increasing concentrations of
CAS 754 or SIN-1 were infused locally into autoperfused segments of
cat ileum at 30 min intervals. Baseline epithelial permeability
(blood to lumen clearance of 51Cr-EDTA) was not affected by CAS 754
whereas vascular protein clearance was reduced. The latter effect
could almost entirely be explained by a decrease in intestinal
capillary hydrostatic pressure. Therefore, in some experiments venous
pressure was elevated and the microvascular reflection coefficient
for total proteins was estimated at filtration-independent rates.
This direct measurement of microvascular permeability was unaffected
by exogenous nitric oxide. CAS 754 did not increase permeability
across monolayers of endothelial or epithelial cells and did not
cause cell injury. Next, we assessed the possibility that excess
nitric oxide may be detrimental, but only in inflamed intestine, by
infusing CAS 754 with platelet-activating factor; the latter directly
increases microvascular and mucosal permeability. CAS 754 did not
exacerbate, but rather reduced, PAF-induced rise in microvascular and
mucosal permeability. These results suggest that high concentrations
of nitric oxide do not cause breakdown of mucosal or microvascular
barrier integrity under normal or inflammatory conditions.
Received 23 June 1994; accepted in final form 20 February 1995.
APS Manuscript Number G240-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.