INDUCIBLE NITRIC OXIDE AND PULMONARY INFECTION

Nitric oxide (NO) is an endogenously produced vasodilator which modulates systemic and pulmonary blood flow through the actions of cyclic guanylate monophosphate (cGMP) on vascular smooth muscle.1-4 Non-haemodynamic properties of NO include the modulation of platelet inhibition, neurotransmission, hormone release, and cell growth. Under physiological circumstances the basal production of NO is regulated by constitutive forms of the enzyme NO synthase (cNOS). Under conditions of chemical and mechanical stress increased NO production is detectable, produced primarily via an inducible NOS isoform (iNOS).5 6 Evidence has accumulated that NO is implicated in the pathogenesis of sepsis and septic shock and may contribute to the development of multiple organ dysfunction. Firstly, iNOS has been isolated from human neutrophils in urinary sepsis7 and from alveolar macrophages in sepsis induced acute lung injury (ALI).8Secondly, NO is known to influence the inflammatory response through actions on both innate and adaptive immune systems.9Thirdly, non-specific cNOS and iNOS inhibition using novel pharmacological …