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Enhanced mucosal permeability and nitric oxide synthase activity in jejunum of mast cell deficient mice
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  1. S Komatsu,
  2. M B Grisham,
  3. J M Russell,
  4. D N Granger
  1. Department of Physiology, LSU Medical Center, 1501 Kings Highway, Shreveport, Louisiana 71130–3932, USA
  1. Dr D N Granger.

Abstract

Background—Recent reports have described a modulating influence of nitric oxide (NO) on intestinal mucosal permeability and have implicated a role for mast cells in this NO mediated process.

Aims—To assess further the contribution of mast cells to the mucosal permeability changes elicited by the NO synthase (NOS) inhibitor NG-nitro-l-arginine methylester (l-NAME), using mast cell deficient (W/WV) and mast cell replete mice (+/+).

Methods—Chromium-51 EDTA clearance (from blood to jejunal lumen), jejunal NOS and myeloperoxidase (MPO) activities, and plasma nitrate/nitrite levels were monitored.

Results—The increased EDTA clearance elicited by intraluminal l-NAME in W/WV mice (4.4-fold) was significantly greater than the response observed in control (+/+) mice (1.8-fold). The exacerbated response in W/Wv mice was greatly attenuated by pretreatment with either dexamethasone (1.3-fold) or the selective inducible NOS inhibitor, aminoguanidine (1.4-fold), and partially attenuated by the mast cell stabiliser, lodoxamide (2.9-fold). Jejunal inducible NOS activity was significantly higher in W/WV than in +/+ mice, while jejunal MPO was lower in W/WV mice than in +/+ mice, suggesting that the higher inducible NOS in W/WV does not result from the recruitment of inflammatory cells into the gut. The higher inducible NOS activity in the jejunum of W/WV was significantly reduced by dexamethasone treatment.

Conclusions—Our results suggest that mast cells normally serve to inhibit inducible NOS activity tonically in the gut and that inhibitors of NOS elicit a larger permeability response when this tonic inhibitory influence is released by mast cell depletion.

  • aminoguanidine
  • c-kit
  • dexamethasone
  • epithelium
  • neutrophils

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