, Volume 53, Issue 9, pp 442-452

Chronic blockade of nitric oxide biosynthesis in rats: effect on leukocyte endothelial interaction and on leukocyte recruitment

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Abstract.

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 β2 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.

Received 14 May 2003; returned for revision 20 June 2003; accepted by N. Boughton-Smith 4 February 200