ROLE OF NITRIC-OXIDE IN INDUCTION OF INFLAMMATORY FLUID SECRETION BY THE MUCOSE OF THE FELINE GALLBLADDER

Background & Aims: Nitric oxide is synthesized from L-arginine and is metabolized to nitrate and nitrite. This study evaluates the effects o f a pharmacological blockade of NO synthesis on fluid transport by the inflamed gallbladder mucosa. Methods: Experiments were performed in c ats with cholecystitis and in control animals. NO synthase activity wa s measured in gallbladder tissue; the enzyme was characterized by immu noblotting techniques and localized by immunofluorescence. Fluid trans port, and release of nitrate and nitrite by the gallbladder mucosa and bite and bile salt secretion from the liver were registered simultane ously in vivo. Results: Fluid secretion in inflamed gallbladders was r eversed to a net absorption in response to the NO synthase blockers N- omega-nitro-L-arginine and aminoguanidine, and formation of nitrate wa s reduced. The effects were reversed by L-arginine. Increased levels o f inducible NO synthase in inflamed gallbladders were shown by immunob lotting, by immunofluorescence (mainly in macrophages), and by Ca2+-in dependent [H-3]citrulline formation from [3H]arginine. The NO synthase blockers had no effect on gallbladder fluid transport in normal gallb ladders. Conclusions: Increased levels of inducible NO synthase activi ty are shown in inflamed gallbladders, and a pharmacological blockade of this enzyme blocks fluid secretion and decreases nitrate release fr om the mucosa.