title: Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications.
abstract: Aneurysmal subarachnoid hemorrhage (SAH) typically carries a poor prognosis. Growing evidence indicates that overabundant production of nitric oxide (NO) may be responsible for a large part of the secondary injury that follows SAH. Although SAH modulates the activity of all three isoforms of nitric oxide synthase (NOS), the inducible isoform, NOS-2, accounts for a majority of NO-mediated secondary injuries after SAH. Here, we review the indispensable physiological roles of NO that must be preserved, even while attempting to downmodulate the pathophysiologic effects of NO that are induced by SAH. We examine the effects of SAH on the function of the various NOS isoforms, with a particular focus on the pathological effects of NOS-2 and on the mechanisms responsible for its transcriptional upregulation. Finally, we review interventions to block NOS-2 upregulation or to counteract its effects, with an emphasis on the potential therapeutic strategies to improve outcomes in patients afflicted with SAH. There is still much to be learned regarding the apparently maladaptive response of NOS-2 and its harmful product NO in SAH. However, the available evidence points to crucial effects that, on balance, are adverse, making the NOS-2/NO/peroxynitrite axis an attractive therapeutic target in SAH.
authors: Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
authors: Sana
authors: S
authors: Iqbal
authors: Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
authors: Erik G
authors: EG
authors: Hayman
authors: Department of Anesthesiology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
authors: Caron
authors: C
authors: Hong
authors: Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
authors: Jesse A
authors: JA
authors: Stokum
authors: Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
authors: David B
authors: DB
authors: Kurland
authors: Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
authors: Volodymyr
authors: V
authors: Gerzanich
authors: Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, Maryland, USA; Department of Pathology, School of Medicine, University of Maryland, Baltimore, Maryland, USA; Department of Physiology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
authors: J Marc
authors: JM
authors: Simard
keywords: Heparin; NOS-1; NOS-2; NOS-3; nitric oxide (NO); subarachnoid hemorrhage (SAH)