Cellular pathways of mast cell- and capsaicin-sensitive nerve-evoked ileal submucosal arteriolar dilations

This study characterized mast cell- and capsaicin-sensitive sensory nerve vasodilator mechanisms regulating submucosal arterioles in the guinea pig ileum. The outside diameter of arterioles in in vitro submucosal preparations from milk-sensitized guinea pigs was monitored using videomicroscopy. Superfusion of the cow's milk protein, beta-lactoglobulin (beta-Lg; 5 microM), evoked large dilations, which became completely desensitized. beta-Lg-evoked dilations were blocked by pyrilamine or NG-monomethyl-L-arginine plus indomethacin but not by TTX. Electron microscopic studies revealed that mast cells, in preparations receiving beta-Lg, demonstrated significant reductions of the dispersed and intact granule areas compared with preparations not exposed to beta-Lg. Paired experiments were conducted to determine if capsaicin-sensitive, nerve-evoked responses involved mast cell degranulation. One preparation received capsaicin (200 nM) followed by beta-Lg (5 microM); the other preparation received the drugs in reverse order. Prior treatment with capsaicin or beta-Lg had no effect on subsequent dilations evoked by the alternate treatment. Electron microscopy showed that nerve-arteriole associations were 10 times closer than nerve-mast cell associations. Mast cell numbers were not increased by milk sensitization. These findings suggest that mast cell- and capsaicin-sensitive nerve-evoked vasodilator mechanisms act independently in a model in which mast cell numbers are not increased.