title: Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase.
abstract: Mice deficient in inducible nitric oxide synthase (iNOS) were generated to test the idea that iNOS defends the host against infectious agents and tumor cells at the risk of contributing to tissue damage and shock. iNOS-/-mice failed to restrain the replication of Listeria monocytogenes in vivo or lymphoma cells in vitro. Bacterial endotoxic lipopolysaccharide (LPS) caused shock and death in anesthetized wild-type mice, but in iNOS-/-mice, the fall in central arterial blood pressure was markedly attenuated and early death averted. However, unanesthetized iNOS-/-mice suffered as much LPS-induced liver damage as wild type, and when primed with Propionobacterium acnes and challenged with LPS, they succumbed at the same rate as wild type. Thus, there exist both iNOS-dependent and iNOS-independent routes to LPS-induced hypotension and death.
authors.affiliation: Beatrice and Samuel A. Seaver Laboratory, Department of Medicine, Cornell University Medical College, New York, New York 10021, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: MacMicking
authors.forename: C
authors.initials: C
authors.lastname: Nathan
authors.forename: G
authors.initials: G
authors.lastname: Hom
authors.forename: N
authors.initials: N
authors.lastname: Chartrain
authors.forename: D S
authors.initials: DS
authors.lastname: Fletcher
authors.forename: M
authors.initials: M
authors.lastname: Trumbauer
authors.forename: K
authors.initials: K
authors.lastname: Stevens
authors.forename: Q W
authors.initials: QW
authors.lastname: Xie
authors.forename: K
authors.initials: K
authors.lastname: Sokol
authors.forename: N
authors.initials: N
authors.lastname: Hutchinson
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism*; D001483:Base Sequence; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase; D012772:Shock, Septic / Q000378:metabolism*
chemical_list: D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases