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Mechanisms of nitrate tolerance: potential roles of folate
Author(s) -
Bellisarii F. Iachini,
Gallina S.,
Zimarino M.,
De Caterina R.
Publication year - 2003
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2003.01239.x
Subject(s) - mechanism (biology) , medicine , folic acid , mechanism of action , intracellular , intensive care medicine , oxidative stress , disease , pharmacology , bioinformatics , chemistry , biology , biochemistry , philosophy , epistemology , in vitro
More than 100 years since their introduction in cardiovascular therapy, nitrates continue to be widely used in ischaemic heart disease despite incomplete knowledge of their intimate mechanism of action. Particularly, the development of a progressive attenuation of their efficacy over prolonged use (tolerance) continues to be the subject of current investigation. Newer findings point to the role of increased intracellular oxidative stress as a mechanism for tolerance and to folic acid derivatives as pharmacologic means to attenuate its development. This paper reviews nitrate mechanism of action, the history of nitrate tolerance and newer findings related to the use of folate to prevent this phenomenon.