INHIBITORS OF NITRIC-OXIDE SYNTHASE SELECTIVELY REDUCE FLOW IN TUMOR-ASSOCIATED NEOVASCULATURE
INHIBITORS OF NITRIC-OXIDE SYNTHASE SELECTIVELY REDUCE FLOW IN TUMOR-ASSOCIATED NEOVASCULATURE
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DOI：
10.1111/j.1476-5381.1992.tb13412.x
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发表时间：
1992-12-01
影响因子：
7.3
通讯作者：
PIPER, PJ
中科院分区：
文献类型：
--
作者：
ANDRADE, SP;HART, IR;PIPER, PJ
1 已经研究了 L-精氨酸类似物、N(G)-硝基-L-精氨酸甲酯 (L-NAME) 和 N(G)-单甲基-L-精氨酸 (L-NMMA) 以及亚甲蓝对小鼠腺癌和黑色素瘤血流的影响。2 Balb/c 和 C57/BL 小鼠体内的海绵植入物用于容纳增殖的肿瘤细胞，同时洗掉 Xe-133用于评估植入海绵中的局部血流。3一氧化氮（NO）的药理学抑制减少了两种肿瘤中的血流，但通过施用L-精氨酸逆转了这种效果。4与此形成鲜明对比的是，这些相同的NO抑制剂对海绵诱导的非肿瘤性肉芽组织中的血流的影响可以忽略不计。5这些结果强烈表明：（a）肿瘤血管中的血流受到一氧化氮的调节，一氧化氮在肿瘤组织中维持扩张器张力； (b) NO抑制剂的收缩活性（通过Xe-133的t 1/2的增加来监测）可能归因于这种扩张张力的消除； (c) 肿瘤脉管系统中描述的许多异常，例如对血管活性介质的反应性低下或无反应以及最大血管舒张，可能是由于癌症中NO合成的增加所致。
1 The effects of L-arginine analogues, N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-monomethyl-L-arginine (L-NMMA) and methylene blue on blood flow in a murine adenocarcinoma and melanoma have been investigated.2 Sponge implants in Balb/c and C57/BL mice were used to host proliferating tumour cells while the washout of Xe-133 was employed to assess local blood flow in the implanted sponges.3 Pharmacological inhibition of nitric oxide (NO) reduced blood flow in both tumours but this effect was reversed by administration Of L-arginine.4 In marked contrast, the effect of these same NO inhibitors on the blood flow in sponge-induced non-neoplastic granulation tissue was negligible.5 These results strongly suggest that: (a) flow in tumour vessels is modulated by nitric oxide which maintains a dilator tone in neoplastic tissue; (b) the constrictor activity (as monitored by an increase in t 1/2 of Xe-133) of NO inhibitors may be attributed to the removal of such dilator tone; (c) many of the abnormalities described in tumour vasculature, such as hyporeactivity or unresponsiveness to vasoactive mediators and maximum vasodilatation, may be due to an increase in NO synthesis in cancers.