Comparison of the NO and HNO Donating Properties of Diazeniumdiolates:  Primary Amine Adducts Release HNO in Vivo

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.

Xerogel Optical Sensor Films for Quantitative Detection of Nitroxyl

“…Despite similar rates of donor decomposition, 27 generation of equivalent HNO concentrations required significantly larger concentrations of IPA/NO. Such a trend is consistent with previous reports of decreased metmyoglobin reductive nitrosylation efficiency by equimolar amounts of IPA/NO and Angeli's salt, 25 and may be attributed to the concurrent formation of NO that is both formed competitively with HNO and scavenges existing HNO from solution. 13 …”

“…The concentrations of IPA/NO stock solutions were determined prior to each experiment by monitoring absorbance at 250 nm (ε = 10000 M −1 cm −1 ). 25 …”

“…The resulting HNOsensing microtitre plates were used to quantify HNO and confirm the pH-dependent nature of nitroxyl generation from a recently described HNO/NO donor compound, sodium-1-(isopropylamino)diazene-1-ium-1,2-diolate (IPA/NO). [23][24][25] …”

Generation of nitroxyl by heme protein-mediated peroxidation of hydroxylamine but not N-hydroxy-L-arginine

“…Recently, a commercially available chemiluminescence system (Sievers NO Analyzer, Ionics, Boulder, CO) was shown to also detect HNO in a GSHdependent manner [38]. Therefore, production of HNO during peroxidation of NH 2 OH or NOHA was examined by performing the reaction in the helium-purged reaction vessel of the analyzer.…”

Photoinduced Upregulation of Calcitonin Gene-Related Peptide in A549 Cells through HNO Release from a Hydrophilic Photocontrollable HNO Donor

“…13) Vasodilating action of HNO has been reported; the mechanism is not clear, but there are many possibilities, including soluble guanylate cyclase (sGC) upregulation, 14,15) and K + channel activation, 16,17) which are different from those in the case of NO. It has also been suggested 18,19) that the mechanism of vasodilation by HNO partly involves a pathway mediated by calcitonin gene-related peptide (CGRP). CGRP is a neuropeptide consisting of 37 amino acids, produced by alternative mRNA splicing of the calcitonin gene, and shows vasodilatory action and ionotropic and chronotropic activities.…”