Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently demonstrated that inhibitors of nitric oxide (NO) production cause a dramatic increase in leukocyte adherence and emigration in postcapillary venules. The objective of this study was to assess whether inhibition of NO production leads to vascular protein leakage and increased microvascular permeability in feline small intestine and to determine whether adherent leukocytes contribute to these responses. Whereas NG-nitro-L-arginine methyl ester (L-NAME) produced fivefold increases in microvascular fluid and protein fluxes, capillary pressure remained unchanged. In some experiments, venous pressure was elevated and the microvascular reflection coefficient for total proteins (sigma d) was estimated from lymph to plasma protein concentration ratio at high capillary filtration rates. L-NAME infusion increased 1 - sigma d (permeability index) from a control value of 0.21 +/- 0.02 to 0.41 +/- 0.07. All of the L-NAME-induced microvascular alterations were completely reversed by nitroprusside. Some animals were pretreated with a monoclonal antibody (MoAb IB4) directed against the leukocyte adhesion glycoprotein complex CD11/CD18. MoAb IB4 did not prevent the initial rise in vascular protein leakage but greatly attenuated the later (30-60 min) phase of enhanced vascular protein leakage. Local intra-arterial infusion of the NO synthesis inhibitor L-NAME (0.025 mumol.ml-1.min-1) produced a profound increase in leukocyte adhesion in postcapillary venules that was partly reversed by sodium nitroprusside administration (0.025 mumol.ml-1.min-1). These results suggest that inhibition of NO production by vascular endothelium leads to a reversible increase in microvascular protein efflux that is mediated by both leukocyte-dependent and -independent mechanisms.
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PMID:Nitric oxide modulates microvascular permeability. 153 22

The objective of this study was to determine whether endogenous nitric oxide (NO) inhibits leukocyte adhesion to vascular endothelium. This was accomplished by superfusing a cat mesenteric preparation with inhibitors of NO production, NG-monomethyl-L-arginine (L-NMMA) or NG-nitro-L-arginine methyl ester (L-NAME), and observing single (30-microns diameter) venules by intravital video microscopy. Thirty minutes into the superfusion period the number of adherent and emigrated leukocytes, the erythrocyte velocity, and the venular diameter were measured; venular blood flow and shear rate were calculated from the measured parameters. The contribution of the leukocyte adhesion glycoprotein CD11/CD18 was determined using the CD18-specific monoclonal antibody IB4. Both inhibitors of NO production increased leukocyte adherence more than 15-fold. Leukocyte emigration was also enhanced, whereas venular shear rate was reduced by nearly half. Antibody IB4 abolished the leukocyte adhesion induced by L-NMMA and L-NAME. Incubation of isolated cat neutrophils with L-NMMA, but not L-NAME, resulted in direct upregulation of CD11/CD18 as assessed by flow cytometry. Decrements in venular shear rate induced by partial occlusion of the superior mesenteric artery in untreated animals revealed that only a minor component of L-NAME-induced leukocyte adhesion was shear rate-dependent. The L-NAME-induced adhesion was inhibited by L-arginine but not D-arginine. These data suggest that endothelium-derived NO may be an important endogenous modulator of leukocyte adherence and that impairment of NO production results in a pattern of leukocyte adhesion and emigration that is characteristic of acute inflammation.
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PMID:Nitric oxide: an endogenous modulator of leukocyte adhesion. 167 86