Comparison of the NO and HNO donating properties of diazeniumdiolates: primary amine adducts release HNO in Vivo

J Med Chem. 2005 Dec 29;48(26):8220-8. doi: 10.1021/jm050151i.

Abstract

Diazeniumdiolates, more commonly referred to as NONOates, have been extremely useful in the investigation of the biological effects of nitric oxide (NO) and related nitrogen oxides. The NONOate Angeli's salt (Na(2)N(2)O(3)) releases nitroxyl (HNO) under physiological conditions and exhibits unique cardiovascular features (i.e., positive inotropy/lusitropy) that may have relevance for pharmacological treatment of heart failure. In the search for new, organic-based compounds that release HNO, we examined isopropylamine NONOate (IPA/NO; Na[(CH(3))(2)CHNH(N(O)NO]), which is an adduct of NO and a primary amine. The chemical and pharmacological properties of IPA/NO were compared to those of Angeli's salt and a NO-producing NONOate, DEA/NO (Na[Et(2)NN(O)NO]), which is a secondary amine adduct. Under physiological conditions IPA/NO exhibited all the markers of HNO production (e.g., reductive nitrosylation, thiol reactivity, positive inotropy). These data suggest that primary amine NONOates may be useful as HNO donors in complement to the existing series of secondary amine NONOates, which are well-characterized NO donors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Azo Compounds / chemistry*
  • Calcitonin Gene-Related Peptide / blood
  • Cardiovascular System / drug effects
  • Cell Survival
  • Cells, Cultured
  • Cricetinae
  • Cricetulus
  • Cyclic GMP / blood
  • Dogs
  • Glutathione / chemistry
  • Hemodynamics / drug effects
  • Hydrazines / chemistry
  • Hydrazines / pharmacology
  • Lethal Dose 50
  • Male
  • Nitric Oxide Donors / chemistry*
  • Nitrites / chemistry
  • Nitrites / pharmacology
  • Nitrogen Oxides / chemistry*
  • Nitrogen Oxides / pharmacology
  • Uric Acid / chemistry

Substances

  • 1-isopropyldiazen-1-ium-1,2-diolate
  • Azo Compounds
  • Hydrazines
  • Nitric Oxide Donors
  • Nitrites
  • Nitrogen Oxides
  • diazeniumdiolate
  • oxyhyponitrite
  • Uric Acid
  • 1,1-diethyl-2-hydroxy-2-nitrosohydrazine
  • Glutathione
  • nitroxyl
  • Cyclic GMP
  • Calcitonin Gene-Related Peptide