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Inhibitors of nitric oxide synthase selectively reduce flow in tumour‐associated neovasculature
Author(s) -
Andrade Silvia P.,
Hart Ian R.,
Piper Priscilla J.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb13412.x
Subject(s) - dilator , nitric oxide , methylene blue , sponge , nitric oxide synthase , blood flow , vasodilation , chemistry , arginine , pharmacology , blood vessel , granulation tissue , endocrinology , medicine , biochemistry , biology , wound healing , immunology , botany , amino acid , photocatalysis , catalysis
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 133 Xe 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 ½ of 133 Xe) 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.