Nitric oxide in hepatic encephalopathy and hyperammonemia.

Chronic alcoholism, viral hepatitis or hepatotoxic drug overdose result in liver dysfunction which may lead to a neuropsychiatric disorder termed hepatic encephalopathy (HE). Although, the exact molecular mechanisms underlying the pathophysiology of HE are not known, excitatory/inhibitory neurotransmitter imbalance leading to dysfunction of the glutamate-nitric oxide (NO) system is thought to play a major role. Activation of the NMDA subtype of glutamate receptors leads to increase in intracellular calcium, which initiates several calcium-dependent processes including NO formation. NO is a gaseous, highly reactive, freely diffusible molecule with a short half-life. Recent studies demonstrate increased expression of the neuronal isoform of NO synthase (NOS) and the uptake of L-arginine (the obligate precursor of NO) in both chronic and acute HE. Hyperammonemia associated with liver dysfunction results in increased NO, which may lead to learning and memory impairments and cerebral edema commonly seen, particularly in acute hyperammonemia.