Nitric Oxide In Preconditioning

NO is produced in brain by 3 isoforms of nitric oxide synthase (NOS): neuronal (nNOS), endothelial (eNOS), and inducible NOS (iNOS). NO is an important mediator of cell-to-cell communication and regulator of cerebral blood flow and metabolism (57). An increase in NO production, first by nNOS in neurons and later by iNOS in glial cells, has been implicated in cell death after cerebral ischemia (58,59). However, under certain conditions, NO might also induce preconditioning. For example, NOS inhibitors have been shown to abolish tolerance induction by hypoxia (60), transient focal ischemia (61), and LPS (62). Further, iNOS is induced by volatile anesthetics, and its blockage inhibits anesthetic preconditioning (37). NO might contribute to tolerance induction via activation of Ras/ERK and Pl3-kinase/Akt neuroprotective signaling pathways (57).

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