The role of L-arginine metabolism in neurocritical care patients

Abstract

Nitric oxide is an important mediator of vascular autoregulation and is involved in pathophysiological changes after acute neurological disorders. Nitric oxide is generated by nitric oxide synthases from the amino acid L-arginine. L-arginine can also serve as a substrate for arginases or lead to the generation of dimethylarginines, asymmetric dimethylarginine, and symmetric dimethylarginine, by methylation. Asymmetric dimethylarginine is an endogenous inhibitor of nitric oxide synthase and can lead to endothelial dysfunction. This review discusses the role of L-arginine metabolism in patients suffering from acute and critical neurological disorders often requiring neuro-intensive care treatment. Conditions addressed in this review include intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, and traumatic brain injury. Recent therapeutic advances in the field are described including current randomized controlled trials for traumatic brain injuries and hemorrhagic stroke.

Keywords: arginine; brain injuries; traumatic; cerebral hemorrhage; dimethylarginine; nitric oxide; stroke; subarachnoid hemorrhage.

Figure 1

The flow chart depicts key pathways of L-arginine metabolism and endogenous mechanisms of interference. ADMA: Asymmetric dimethylarginine; hCAT-2B: human cationic amino acid transporter 2B; NO: nitric oxide; NOS: nitric oxide synthase; SDMA: symmetric dimethylarginine.

Figure 2

Potential alterations of the L-arginine metabolism in neurocritical care patients and downstream pathophysiological consequences are illustrated. ADMA: Asymmetric dimethylarginine; NF-κB: nuclear factor κB; NO: nitric oxide; NOS: nitric oxide synthase; ROS: reactive oxygen species.