Nitric oxide in sepsis: pathophysiological mechanisms and therapeutic implications

Sepsis is a life-threatening syndrome defined by organ dysfunction arising from a dysregulated host response to infection. In its more severe forms, it may progress to multiple organ failure and is associated with a substantial increase in mortality risk. Nitric oxide (NO), a gaseous signaling mediator, has attracted attention because of its context-dependent roles in both physiological regulation and pathological processes. NO participates in intracellular signaling pathways and modulates protein function through post-translational mechanisms. In patients with sepsis, altered NO production has been closely linked to circulatory shock, vascular hyporeactivity, and multiple organ dysfunction, with particularly significant effects on cardiovascular and renal systems. Despite extensive investigation, the precise role of NO at different stages of sepsis remains incompletely defined. Clarifying the temporal and mechanistic aspects of NO dysregulation may help determine its utility as a biomarker and as a potential therapeutic target. Future clinical strategies should focus on modulating excessive NO activity without compromising its essential physiological functions, thereby improving the translational feasibility and clinical applicability of NO-directed interventions.