Enhanced mucosal permeability and nitric oxide synthase activityin jejunum of mast cell deficient mice

Background—Recent reports have described amodulating influence of nitric oxide (NO) on intestinal mucosalpermeability and have implicated a role for mast cells in this NOmediated process.
Aims—To assess further the contribution of mastcells to the mucosal permeability changes elicited by the NO synthase(NOS) inhibitor N^G-nitro-L-arginine methylester(L-NAME), using mast cell deficient (W/W^V) andmast cell replete mice (+/+).
Methods—Chromium-51 EDTA clearance (from blood tojejunal lumen), jejunal NOS and myeloperoxidase (MPO) activities, andplasma nitrate/nitrite levels were monitored.
Results—The increased EDTA clearance elicited byintraluminal L-NAME in W/W^V mice (4.4-fold) wassignificantly greater than the response observed in control (+/+) mice(1.8-fold). The exacerbated response in W/W^v mice wasgreatly 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 inW/W^V than in +/+ mice, while jejunal MPO was lower inW/W^V mice than in +/+ mice, suggesting that the higherinducible NOS in W/W^V does not result from the recruitmentof inflammatory cells into the gut. The higher inducible NOS activityin the jejunum of W/W^V was significantly reduced bydexamethasone treatment.
Conclusions—Our results suggest that mast cellsnormally serve to inhibit inducible NOS activity tonically in the gutand that inhibitors of NOS elicit a larger permeability response when this tonic inhibitory influence is released by mast cell depletion.

Keywords:aminoguanidine; c-kit; dexamethasone; epithelium; neutrophils