Controversial Role of Nitric Oxide in Hepatic Structural and Functional Injury

Abstract Nitric oxide (NO) may regulate hepatic metabolism directly by causing alterations in hepatocellular (hepatocyte and Kupffer cell) metabolism and function or indirectly as a result of its yasodilator properties. NO may be released from the hepatic vascular endothelìum, platelets,nerve endings, mast cells, and Kupffer cells as a response to various stimuli such as endotoxemia,ischemia-reperfusìon injury, and circulatory shock It is synthesized by nitric oxide synthase (NOS),which has three distinguishable ìsoforms: NOS-l (ncNOS) a constitutive isoform originally isolated from neuronal sources; NOS-2 (iNOS), an inducible isoform that may generate large quantities of NO and may be induced in a variety of cell types throughout the body by the action of inflammatory stimuli; and NOS-3 (ecNOS), a constitutiye isoform originally located in endothelial cells. It is believed that Kupffer cells are the main source of NO during endotoxemic shock and that selective inhibition of this stimulation may have future beneficial therapeutic implications. NO may possess both cytoprotectìve and cytotoxìc properties depending on the amount and the isoform of NOS by which it is produced.The mechanisms by which these properties are regulated are important in the maintenance of whole body homeostasis and remain to be elucidated