Inflammatory and Vascular Alterations in Sepsis: The Role of Nitric Oxide- Dependent Mechanisms

Sepsis and septic shock continue to be a major cause of morbidity and mortality in critically ill patients. During the onset of sepsis, a massive inflammatory reaction is mediated via cell-derived cytokines and chemokines that target end-organ receptors in response to injury or infection. Polymorphonuclear leucocytes are critical effector cells during the inflammatory process and their migration to the infectious focus is extremely important for the local control of bacterial growth and consequently for the prevention of bacterial dissemination. In addition to the inflammatory process, sepsis and septic shock cause a profound loss in the peripheral vasomotor tone resulting in a huge decrease in the peripheral resistance, a central event in the derangement of hemodynamic and perfusional parameters. Nitric oxide (NO) is a simple molecule produced by numerous cell types that has been implicated in a wide range of physiological and pathological processes, exerting both detrimental and beneficial effects. It is an important modulator of neutrophil adherence and activation, of cardiovascular homeostasis and end organ perfusion. The induction of the inducible isoform of NO synthase leads to an increased NO production which is involved both in the impairment of neutrophil migration and in the cardiovascular disfunction present in sepsis and septic shock. Thus, a better knowledge of the role of NO in the inflammatory, cardiovascular and immune aspects of sepsis may provide us with more efficient therapeutic alternatives to treat sepsis and septic shock.