Nilsson B, Delbro D, Hedin L, Conradi N, Thune A, Friman S, Wennmalm A, Yan Z Q, Svanvik J
Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
Gastroenterology. 1996 Feb;110(2):598-606. doi: 10.1053/gast.1996.v110.pm8566609.
BACKGROUND & AIMS: 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.
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.
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.
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.
一氧化氮由L-精氨酸合成，并代谢为硝酸盐和亚硝酸盐。本研究评估一氧化氮合成的药理学阻断对炎症性胆囊黏膜液体转运的影响。
在患有胆囊炎的猫和对照动物身上进行实验。测定胆囊组织中的一氧化氮合酶活性；通过免疫印迹技术对该酶进行表征，并通过免疫荧光进行定位。在体内同时记录胆囊黏膜的液体转运以及硝酸盐和亚硝酸盐的释放，以及肝脏的胆汁和胆盐分泌。
炎症性胆囊中的液体分泌在使用一氧化氮合酶阻滞剂Nω-硝基-L-精氨酸和氨基胍后转变为净吸收，并且硝酸盐的形成减少。L-精氨酸可逆转这些作用。通过免疫印迹、免疫荧光（主要在巨噬细胞中）以及由[3H]精氨酸形成不依赖钙的[3H]瓜氨酸，显示炎症性胆囊中诱导型一氧化氮合酶水平升高。一氧化氮合酶阻滞剂对正常胆囊的胆囊液体转运没有影响。
炎症性胆囊中显示出诱导型一氧化氮合酶活性水平升高，对该酶的药理学阻断可阻断液体分泌并减少黏膜中硝酸盐的释放。
