97th DOG Annual Meeting 1999

P534

MODULATION OF LEUKOCYTE ADHESION BY NITRIC OXIDE ANTAGONISTS

H. Baatz, U. Pleyer, C Hartmann

Aim: To examine the effects of early and late administration of nitric oxide synthase (NOS) inhibitors on leukocyte adhesion in endotoxin-induced uveitis (EIU).

Methods: Uveitis was induced in Lewis rats (n = 124) by endotoxin administration. Six groups of Rats were studied: group 1: healthy, untreated (controls); group 2: endotoxin-induced uveitis, untreated; group 3: endotoxin-induced uveitis, aminoguanidine (AG, 100 mg/kg body weight) at the time of endotoxin administration; group 4: AG 8 hours after endotoxin injection; group 5: AG at the time of endotoxin administration and 8 hours thereafter and group 6: L-NAME (75 mg/kg body weight) at the time of LPS administration. Leukocyte-endothelium interaction in iris venules was evaluated at 2, 4, 8, 16, 24 and 48 hours after endotoxin injection.

Results: At 2 hours after the induction of uveitis, more rolling leukocytes were detected in the AG and L-NAME-treated group than in untreated EIU (4.8 ± 0.31 and 9.83 ± 0.64 vs. 2.85 ± 0.37 %, mean ± SEM, p < 0.01). However, at 16 hours the percentage of rolling leukocytes was significantly reduced in all groups which had received AG (LPS: 8.08 ± 0.37%; LPS/AG 0h: 3.78 ± 0.25%; LPS/AG 8h: 5.34 ± 0.3%; LPS/AG 0+8h: 3.86 ± 0.31%). L-NAME enhanced leukocyte rolling even at 24 hours after LPS (12.38 ± 0.64%). Early treatment of EIU with AG significantly reduced the number of firmly adherent leukocytes at 4, 8 and 24 hours (306 ± 13 vs. 571 ± 41, 228 ± 12 vs. 345 ± 19 and 240 ± 14 vs. 469 ± 23 cells/mm², respectively). L-NAME inhibited LPS-induced sticking of leukocytes at all observed time points.

Conclusions: In EIU, administration of NOS inhibitors decreases firm adhesion of leukocytes to the vascular endothelium, ameliorating leukocyte infiltration. This effect prevails over enhanced leukocyte rolling, which occurs in the first hours after NOS inhibition.

Dept. of Ophthalmology, Charité, Campus Virchow-Klinikum, D-13353 Berlin


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