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Nitrates and NO release: contemporary aspects in biological and medicinal chemistry

Domenii publicaţii > Ştiinţe medicale + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Thatcher G.R., Nicolescu A.C., Bennett B.M., Toader V

Editorial: Free Radical Biol. Med., 37(8), p.1122-43, 2004.


Nitroglycerine has been used clinically in the treatment of angina for 130 years, yet important details on the
mechanism of action, biotransformation, and the associated phenomenon of nitrate tolerance remain unanswered. The
biological activity of organic nitrates can be said to be nitric oxide mimetic, leading to recent, exciting progress in
realizing the therapeutic potential of nitrates. Unequivocally, nitroglycerine and most other organic nitrates, including NO-NSAIDs, do not behave as NO donors in the most fundamental action: in vitro activation of sGC to produce cGMP.
The question as to whether the biological activity of nitrates results primarily or exclusively from NO donation will not be satisfactorily answered until the location, the apparatus, and the mechanism of reduction of nitrates to NO are defined.
Similarly, the therapeutic potential of nitrates will not be unlocked until this knowledge is attained. Aspects of the therapeutic and biological activity of nitrates are reviewed in the context of the chemistry of nitrates and the elusive efficient 3electron reduction required to generate NO.

Cuvinte cheie: Nitrati, Monoxid de azot, biotransformare, cGMP, Nitrare, Nitrozare, Radicali liberi // Nitrate, Nitric oxide, Biotransformation, cGMP, Signaling, Nitration, Nitrosation, Free radicals