Enhanced mucosal permeability and nitric oxide synthase activity in jejunum of mast cell deficient mice.
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.


OBJECTIVE
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.
Komatsu
S
S
Department of Physiology, LSU Medical Center, Shreveport 71130-3932, USA.
Grisham
M B
MB
Russell
J M
JM
Granger
D N
DN
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002860:Chromium Radioisotopes; D003907:Dexamethasone / Q000494:pharmacology; D004492:Edetic Acid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D007583:Jejunum / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D002860:Chromium Radioisotopes; D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D003907:Dexamethasone; D004492:Edetic Acid; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D010072:Oxamic Acid; C004479:pimagedine; C021702:lodoxamide ethyl; D019331:NG-Nitroarginine Methyl Ester