Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: iNO

Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: iNONONOates, adducts of NO and various nucleophile moieties, are distinct NO donors that spontaneously and nonenzymatically release NO at predictable rates. The in vivo decomposition studies described in the present report confirm continuous intrapulmonary NO release for at least 12 to 24 h following the exposure of mice to nebulized DETA-NO. Although the mice clearly received a large dose of NO during DETA-NO nebulization, the precise dose remains largely unknown in the absence of actual measurements of DETA-NO concentration in the exposure chamber, the minute ventilation of individual mice, and the physicochemical properties of nebulized DETA-NO. However, given the negative results with iNO exposure, which provided NO in gaseous form at a uniform chamber concentration, the potential factors affecting actual NO delivery by nebulized DETA-NO are less relevant in our model of pneumonia. natural asthma treatment

Intrapulmonary delivery of nebulized DETA-NO in solution/liquid is associated with initial release of dissolved, gaseous, free radical NO’ (unpaired electron), Clearly, a portion of this NO was lost in exhaled breath. This free radical also may react with various other free radicals, such as superoxide radical and macromolecules, including thiols, lipids, and peptides. The resulting products, including peroxynitrite and S-nitrosothiols, are themselves important biological mediators of both physiologic and inflammatory responses.- Indeed, some of the effects ascribed to NO can instead be mediated by such NO-related species. Regardless of these interactions, the ultimate disposal of endogenous and exogenous NO (eg, iNO or from DETA-NO) is thought to be through oxidative metabolism to nitrites/ nitrates (NOx_). For example, nitrates are the final products of the reaction of NO with intravascular hemoglobin as well as the oxidative decomposition of peroxynitrite (ONOO~), through peroxynitrous acid (ONOOH), to the radicals OH* and NO2\ It is notable that despite the significant, sustained elevations of both eNO and plasma levels of NOx~ following exposure to nebulized DETA-NO, the BAL levels of NOx~ remained unchanged. This suggests minimal intrapulmonary oxidation of NO.