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Accelerated intimal hyperplasia and increased endogenous inhibitors for NO synthesis in rabbits with alloxan‐induced hyperglycaemia
Author(s) -
Masuda Hiroshi,
Goto Moritaka,
Tamaoki Satoru,
Azuma Hiroshi
Publication year - 1999
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 - 10.1038/sj.bjp.0702298
Subject(s) - medicine , endocrinology , endothelium , hyperplasia , alloxan , intimal hyperplasia , endogeny , omega n methylarginine , arginine , chemistry , nitric oxide , biochemistry , diabetes mellitus , nitric oxide synthase , smooth muscle , amino acid
We examined whether endogenous inhibitors of NO synthesis are involved in the augmentation of intimal hyperplasia in rabbits with hyperglycaemia induced by alloxan. Four weeks after the endothelial denudation of carotid artery which had been performed 12 weeks after alloxan, the intimal hyperplasia was greatly augmented with hyperglycaemia. The degree of hyperplasia was assessed using three different parameters of histopathological findings as well as changes in luminal area and intima : media ratio. There were positive and significant correlations between intima : media ratio, plasma glucose, and concentrations of N G ‐monomethyl‐ L ‐arginine ( L ‐NMMA) and N G , N G ‐dimethyl‐ L ‐arginine (ADMA) in endothelial cells, that is, the intima : media ratio became greater as plasma glucose and endothelial L ‐NMMA and ADMA were increased. Furthermore, endothelial L ‐NMMA and ADMA were increased in proportion to the increase in plasma glucose. In contrast, there were inverse and significant correlations between cyclic GMP production by carotid artery strips with endothelium and plasma glucose, between cyclic GMP production and endothelial L ‐NMMA and ADMA, and between the intima : media ratio and cyclic GMP production. Exogenously applied L ‐NMMA and ADMA inhibited cyclic GMP production in a concentration‐dependent manner. IC 50 values were determined to be 12.1 μ M for the former and 26.2 μ M for the latter. The cyclic GMP production was abolished after the deliberate removal of endothelium from the artery strips. These results suggest that the augmentation of intimal hyperplasia with hyperglycaemia is closely related to increased accumulation of L ‐NMMA and ADMA with hyperglycaemia, which would result in an accelerated reduction in NO production/release by endothelial cells.British Journal of Pharmacology (1999) 126 , 211–218; doi: 10.1038/sj.bjp.0702298

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