N-G-METHYL-L-ARGININE, AN INHIBITOR OF NITRIC-OXIDE FORMATION, REVERSES IL-2-MEDIATED HYPOTENSION IN DOGS
N-G-METHYL-L-ARGININE, AN INHIBITOR OF NITRIC-OXIDE FORMATION, REVERSES IL-2-MEDIATED HYPOTENSION IN DOGS
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DOI：
10.1152/jappl.1994.76.3.1130
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发表时间：
1994-03-01
影响因子：
3.3
通讯作者：
GRIFFITH, OW
中科院分区：
文献类型：
--
作者：
KILBOURN, RG;OWENSCHAUB, LB;GRIFFITH, OW
N-G-甲基-L-精氨酸，一氧化氮形成抑制剂，逆转犬IL-2介导的低血压。J. Appl.Physiol.76（3）：1130-1137，1994. - 用白细胞介素-2（IL-2）处理犬，研究了一氧化氮生成抑制剂N-G-甲基-L-精氨酸（L-NMA）的作用。对犬给予IL-2导致治疗后3天内出现低血压。低血压的发生与血清中硝酸盐的积累有关，硝酸盐是一氧化氮的稳定分解产物。给予L-NMA可降低血清硝酸盐水平并增加平均动脉压。抗水肿作用具有剂量依赖性，在20 mg/kg剂量下观察到最大作用。连续输注L-NMA（5 mg.kg（-1）.h（-1））可维持平均动脉压48 h，同时给予IL-2。IL-2诱导的淋巴因子激活的杀伤细胞增殖和对犬胶质母细胞瘤靶细胞系的杀肿瘤活性的评价不受L-NMA的影响。这些研究表明，L-NMA可以有效地改善与IL-2给药相关的剂量限制性低血压，而不会对抗肿瘤作用产生不利影响。
N-G-methyl-L-arginine, an inhibitor of nitric oxide formation, reverses IL-2-mediated hypotension in dogs. J. Appl. Physiol. 76(3): 1130-1137, 1994. - The effects of N-G-methyl-L-arginine (L-NMA), an inhibitor of nitric oxide formation, were studied in dogs treated with interleukin-2 (IL-2). The administration of IL-2 to dogs resulted in hypotension within 3 days of treatment. The development of hypotension correlated with accumulation in the serum of nitrate, which is a stable breakdown product of nitric oxide. Administration of L-NMA decreased serum nitrate levels and increased the mean arterial pressure. The antihypotensive effect was dose dependent with a maximum effect observed at a dose of 20 mg/kg. Administration of a continuous infusion of L-NMA (5 mg.kg(-1).h(-1)) maintained the mean arterial pressure for 48 h with concurrent administration of IL-2. Evaluation of IL-2-induced lymphokine-activated killer cell proliferation and tumoricidal activity toward a canine glioblastoma target cell line was unaffected by L-NMA. These studies imply that L-NMA may effectively ameliorate the dose-limiting hypotension associated with administration of IL-2 without adversely affecting the antitumor effects.