Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia: Mice with pneumonia

Discussionxposure to nebulized DETA-NO, a NO donor, is associated with significant, prolonged intrapulmo-nary NO release in mice. In a mouse model of P aeruginosa pneumonia, the intermittent nebuliza-tion of DETA-NO significantly attenuated intrapul-monary bacterial growth. However, a possible in vivo antibacterial effect of exogenous NO was not confirmed during the administration of iNO, which at 40 ppm was associated instead with an increased pulmonary bacterial load. The exposure of P aeruginosa to DETA-NO in vitro demonstrated a direct antibacterial effect. However, an equipotent antibacterial effect was observed in vitro on exposure to the DETA nucleophile moiety alone, which was generated from DETA-NO following the release of all bound NO. Thus, the in vitro and in vivo antibacterial effects of DETA-NO appear to be localized to the DETA moiety and are largely independent of NO. Neither DETA-NO nor iNO had any effect on pulmonary inflammation in mice with pneumonia.
NO is a multifunctional mediator with important homeostatic vascular and immune effects More info flovent inhaler. Recognition of the physiologic pulmonary vascular effects of endogenous NO led to the development of iNO therapy for conditions such as pulmonary hypertension and acute lung injury. Unfortunately, the delivery of iNO therapy is technically challenging because of concerns about ambient levels and health-care giver exposure. Furthermore, since the effects of iNO are transient and are not sustained on withdrawal, iNO must be provided on a continuous basis. Thus, there has been intensive research into alternative strategies for the administration of exogenous NO. Several other NO donors exist, including S-nitrosothiols, nitrovasodilators, and NONOates. Most NO donors do not release NO at predictable rates, being sensitive to local conditions including pH, redox status, thiol levels, and enzymatic degradation.