RATIONALE: NLRs ( @entity377 oligomerisation domain [NOD] proteins containing a @entity368 -rich repeat) are cytosolic pattern recognition receptors. @entity23483 senses @entity6135 -containing peptidoglycan present in gram-negative bacteria, whereas @entity23484 senses the muramyl dipeptide (MDP) present in most organisms. Bacteria are the most common cause of @entity326 , which is characterized clinically by @entity551 resistant to vasopressor agents. In animal models, gram-negative @entity326 is mimicked by lipopolysaccharide (LPS), which signals through @entity1990 ( @entity1990 ) and its adaptor @entity5001 . The role of NLRs in the pathophysiology of @entity326 is not known. OBJECTIVES: To compare the effects of selective @entity23483 agonists with LPS in vivo. METHODS: Vascular smooth muscle cells or whole aortas from wild-type or genetically modified @entity19 were stimulated in vitro with agonists of @entity23483 ( @entity18505 ) or @entity23484 (MDP). Vasoconstriction was measured using wire myography. @entity842 (NO) formation was measured using Griess reaction and NO synthase-II protein by Western blotting. In vivo, blood pressure, heart rate, and urine output were measured in sham-, LPS-, or @entity18505 -treated animals. Biomarkers of end-organ injury, coagulation activation, NO, and cytokines were measured in plasma. MAIN RESULTS: @entity18505 , but not @entity7192 , induced NO synthase-II protein/activity in vascular smooth muscle and vascular hyporeactivity to pressor agents. @entity18505 had no effect on vessels from @entity23483 (-/-) @entity19 , but was active in vessels from @entity1990 (-/-), @entity8932 (-/-), or @entity5001 (-/-) @entity19 . @entity18505 induced @entity551 , increased heart rate, and caused multiple (renal, liver) injury and dysfunction in vivo. CONCLUSIONS: Activation of @entity23483 induces shock and multiple @entity66 .

Selective XXXX agonists cause shock and @entity66 in vivo.

@entity6135 :: ('MESH:D003960', 'Chemical') :: ['diaminopimelic acid'] @entity23484 :: ('257632(Tax:10090)', 'Gene') :: ['NOD2'] @entity66 :: ('MESH:D004194', 'Disease') :: ['organ injury/dysfunction'] @entity368 :: ('CHEBI:25017', 'Chemical') :: ['leucine'] @entity326 :: ('MESH:D012772', 'Disease') :: ['septic shock'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity18505 :: ('MESH:C039537', 'Chemical') :: ['FK565'] @entity7192 :: ('CHEBI:59414', 'Chemical') :: ['MDP'] @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide'] @entity23483 :: ('107607(Tax:10090)', 'Gene') :: ['NOD1'] @entity5001 :: ('17874(Tax:10090)', 'Gene') :: ['MyD88'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['Nitric oxide'] @entity8932 :: ('24088(Tax:10090)', 'Gene') :: ['TLR2'] @entity1990 :: ('21898(Tax:10090)', 'Gene') :: ['TLR4', 'Toll-like receptor 4'] @entity551 :: ('MESH:D007022', 'Disease') :: ['hypotension']
@entity23483 :: (107607(Tax:10090),Gene) :: ['NOD1']
