Role of nitric oxide in induction of inflammatory fluid secretion by the mucosa of the feline gallbladder.
OBJECTIVE
Nitric oxide is synthesized from L-arginine and is metabolized to nitrate and nitrite. This study evaluates the effects of a pharmacological blockade of NO synthesis on fluid transport by the inflamed gallbladder mucosa.


METHODS
Experiments were performed in cats with cholecystitis and in control animals. NO synthase activity was measured in gallbladder tissue; the enzyme was characterized by immunoblotting techniques and localized by immunofluorescence. Fluid transport and release of nitrate and nitrite by the gallbladder mucosa and bile and bile salt secretion from the liver were registered simultaneously in vivo.


RESULTS
Fluid secretion in inflamed gallbladders was reversed to a net absorption in response to the NO synthase blockers N omega-nitro-L-arginine and aminoguanidine, and formation of nitrate was reduced. The effects were reversed by L-arginine. Increased levels of inducible NO synthase in inflamed gallbladders were shown by immunoblotting, by immunofluorescence (mainly in macrophages), and by Ca(2+)-independent [3H]citrulline formation from [3H]arginine. The NO synthase blockers had no effect on gallbladder fluid transport in normal gallbladders.


CONCLUSIONS
Increased levels of inducible NO synthase activity are shown in inflamed gallbladders, and a pharmacological blockade of this enzyme blocks fluid secretion and decreases nitrate release from the mucosa.
Nilsson
B
B
Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
Delbro
D
D
Hedin
L
L
Conradi
N
N
Thune
A
A
Friman
S
S
Wennmalm
A
A
Yan
Z Q
ZQ
Svanvik
J
J
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D001826:Body Fluids / Q000378:metabolism*; D002415:Cats; D002764:Cholecystitis / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005704:Gallbladder / Q000201:enzymology / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D007150:Immunohistochemistry; D009092:Mucous Membrane / Q000201:enzymology / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine
D001647:Bile Acids and Salts; D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; C004479:pimagedine