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Introduction: Previous studies showed that animals chronically treated with NG-nitro-L-arginine methyl ester (L-NAME) have a reduced inflammatory reaction. Now the role of L-NAME treatment (20 mg/Kg/day/14 days) on leukocyte mobilisation was assessed in rats. Methods: In vivo leukocyte recruitment evoked by Bothrops jararaca venom (BjV) and nitrite/nitrate (NO 2 −/NO 3 −; Griess reaction) were evaluated in the air pouch cavity. Haematological parameters were evaluated in the bone marrow and in the peripheral compartment. Microcirculatory blood flow, number of rolling and adhered leukocytes, vascular reactivity and mast cell activity were studied by intravital microscopy. Blood pressure was measured by the tail-cuff method. L-selectin and β 2 integrin expressions on peripheral and bone marrow leukocytes were quantified by flow cytometry. Results: When compared with control rats (D-NAME) L-NAME treated rats had reduced PMN cell infiltrate (50%) and NO 2 −/NO 3 − (27%) in the air pouch cavity. Rolling leukocytes were decreased (70%) in L-NAME-treated animals, which was reversed by topical application of NO donor (SIN-1). BjV stimulation increased the number of rolling and adhered leukocytes only in control rats. Systemic blood pressure, microcirculatory blood flow and microvascular reactivity was not altered by the treatment. Only the vessel response to acetylcholine was delayed in treated rats. Peripheral PMN cells were increased by L-NAME treatment (100%), but the number of bone marrow cells was not altered. The treatment reduced L-selectin expression on circulating leukocytes, by either with (16%) or without (26%) stimulation with BjV; PMN cells were more affected (32–37%). Impairment of L-selectin expression was also verified in bone marrow cells under stimulation with BjV. Conclusions: Results show that this schedule of L-NAME treatment promotes a decrease on L-selectin expression. This effect may promote the standstill of leukocytes in the blood compartment and may be responsible, at least in part, for the observed deficient leukocyte-endothelium interactions with subsequent impairment of leukocyte migration to the inflammatory site.

The influence of aging on neutrophil chemotaxis, chemokinesis, and superoxide production was investigated in rats. Animals of two age groups, 3 to 4 months and 20 to 21 months, were used. Equivalent neutrophil chemotactic responses to N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP), leukotriene B4(LTB4), and bacterial lipopolysaccharide (LPS)‐activated plasma were observed in both groups of animals, with cells suspended in Hanks' balanced salt solution (HBSS). However, cross‐incubation studies in which cells from young adult rats were exposed to plasma from aged donors, then resuspended in HBSS for testing, showed marked changes in the ability of the cells to respond to the chemoattractants. The response to LPS‐activated plasma was reduced, whereas responses to fMLP and LTB4remained unaltered. Previous incubation of the cells with homologous plasma from young donors produced no effect. The inhibitory activity developing with advancing age affected not only chemotaxis but also random movement stimulated by LPS‐activated plasma. The inhibitory activity of chemotaxis and chemokinesis in plasma of aged animals was heat labile (56°), vanished in the presence of a proteolytic enzyme like trypsin, and was maintained after dialysis with 12,000‐Mrretention dialysis tubing. The material did not influence superoxide production by stimulated neutrophils. It is suggested that inhibition of neutrophil locomotion with advancing age is associated with a plasma protein capable of interacting with neutrophil receptors for complement‐derived chemoattractants. The inhibitory substance might influence neutrophil responses to infection and inflammation in the elderly.