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Updated: Aug 21, 2026

Analytical Techniques for Assaying Nitric Oxide Bioactivity
Published on: June 18, 2012
Nitrates and NO release: contemporary aspects in biological and medicinal chemistry
Gregory R J Thatcher1, Adrian C Nicolescu, Brian M Bennett
1Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood Street, Chicago, IL 60612-7231, USA. thatcher@uic.edu
Abstract:
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 3e- reduction required to generate NO.
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