Giraldelo C M, Zappellini A, Muscará M N, De Luca I M, Hyslop S, Cirino G, Zatz R, De Nucci G, Antunes E
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, SP, Brazil.
Eur J Pharmacol. 1994 May 12;257(1-2):87-93. doi: 10.1016/0014-2999(94)90698-x.
Nitro-L-arginine methyl ester (0.15 mumol/paw) significantly reduced both bradykinin- and 5-hydroxytryptamine-induced rat paw oedema. At this dose, L-arginine (L-Arg), D-Arg and nitro-D-arginine methyl ester had no effect on the oedematogenic responses induced by these agents. Nitro-L-arginine methyl ester, nitro-D-arginine methyl ester, L-Arg, D-Arg, L-arginine methyl ester and L-arginine ethyl ester, at the dose of 15 mumol/paw, significantly potentiated both bradykinin- and 5-hydroxytryptamine-induced oedema. This potentiation was not observed in animals treated with both mepyramine and methysergide or in animals chronically treated with compound 48/80. Nitro-L-arginine methyl ester (0.3-3 mM) and L-Arg (0.3-3 mM) released small amounts (< 10%) of histamine from rat peritoneal mast cells when compared to compound 48/80-induced degranulation (> 40%). Histamine release was quantified by radioimmunoassay since nitro-L-arginine methyl ester and L-Arg interfere with the fluorometric assay. The potentiation of paw oedema observed with higher doses of all arginine analogues is caused by in vivo mast cell degranulation and is probably due to the cationic charge of these substances.
硝基-L-精氨酸甲酯（0.15 μmol/爪）可显著减轻缓激肽和5-羟色胺诱导的大鼠爪部水肿。在此剂量下，L-精氨酸（L-Arg）、D-精氨酸和硝基-D-精氨酸甲酯对这些药物诱导的致水肿反应无影响。剂量为15 μmol/爪时，硝基-L-精氨酸甲酯、硝基-D-精氨酸甲酯、L-Arg、D-Arg、L-精氨酸甲酯和L-精氨酸乙酯均显著增强缓激肽和5-羟色胺诱导的水肿。在用美吡拉敏和甲基麦角新碱治疗的动物或用化合物48/80长期治疗的动物中未观察到这种增强作用。与化合物48/80诱导的脱颗粒（>40%）相比，硝基-L-精氨酸甲酯（0.3 - 3 mM）和L-Arg（0.3 - 3 mM）从大鼠腹腔肥大细胞释放的组胺量较少（<10%）。由于硝基-L-精氨酸甲酯和L-Arg会干扰荧光测定法，因此通过放射免疫测定法定量组胺释放。所有精氨酸类似物较高剂量时观察到的爪部水肿增强是由体内肥大细胞脱颗粒引起的，可能是由于这些物质的阳离子电荷所致。
