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Increase in experimental pulmonary metastasis in mice by L‐arginine under inhibition of nitric oxide production by N G ‐nitro‐L‐arginine methyl ester
Author(s) -
Yamamoto Takashi,
Terada Nobuyuki,
Seiyama Akitoshi,
Nishizawa Yasuko,
Akedo Hitoshi,
Kosaka Hiroaki
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980105)75:1<140::aid-ijc21>3.0.co;2-j
Subject(s) - nitric oxide , arginine , endogeny , metastasis , chemistry , nitric oxide synthase , platelet , nitrite , melanoma , pharmacology , biochemistry , medicine , cancer , nitrate , cancer research , amino acid , organic chemistry
As we have previously reported, intraperitoneal injections of N G ‐nitro‐L‐arginine methyl ester [L‐NAME; a competitive inhibitor of nitric oxide (NO) synthase] before and after the injection of B16 melanoma cells through a tail vein increased experimental pulmonary metastasis, while simultaneous injections of L‐arginine (a substrate of NO synthase) at a 20‐fold higher dose synergistically increased pulmonary metastasis. Our present study was intended to elucidate the mechanisms by which L‐NAME alone or together with L‐arginine increases metastasis. Injections of L‐NAME decreased the serum concentration of nitrite plus nitrate (metabolites of NO) by about 50%, which was not reversed by simultaneous injections of L‐arginine. Injections of L‐NAME also decreased the diameter of arterioles and venules by 20–30%, while simultaneous injections of L‐arginine did not show any significant effect. When collagen‐ or ADP‐induced platelet aggregation was examined using platelet‐rich plasma, injections of L‐NAME showed little effects on platelet aggregation, while simultaneous injections of L‐arginine rather suppressed platelet aggregation. B16 melanoma cells produced NO in culture, and L‐NAME (0.2 mM) decreased NO production without effects on viability. Our results suggest that the increased experimental pulmonary metastasis induced by L‐NAME can be ascribed partly to the contraction of arterioles and venules, which is induced by the inhibition of endogenous NO production by L‐NAME, and that the synergistic effect of L‐arginine on metastasis is related to the inhibition of endogenous NO production through unknown mechanisms. Int. J. Cancer 75:140–144, 1998.© 1998 Wiley‐Liss, Inc.