Role of nitric oxide on the increased vascular permeability and neutrophilaccumulation induced by staphylococcal enterotoxin B into the mouse paw

The role of nitric oxide (NO) on the increase in vascular permeability and neutrophil migration induced by staphylococcal enterotoxin B (SEB: 25 mug/p aw) in the mouse was investigated in this study. The NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) [but not its inactive enanti omer N-omega-nitro-D-arginine methyl ester (D-NAME)I, given intravenously ( 25-100 mu moL/kg) or subplantarly (0.25-1.0 mu mol/paw). reduced SEE-induce d paw oedema significantly. A similar response was observed with aminoguani dine, given either intravenously (200-600 mu mol/kg) or subplantarly (2 mu mol/paw). In contrast to paw oedema. the plasma exudation in response to SE E was not affected by the subplantar injection of L-NAME or aminoguanidine. The inhibition of oedema and plasma exudation by systemic treatment with L -NAME or aminoguanidine was reversed by co-injection of the vasodilator ilo prost (0.3 nmol/paw). Subplantar injection of SEE (25 mug/paw) increased by 69% the myeloperoxidase (MPO) activity of SEE-treated paws, indicating the presence of neutrophils. Intravenous (12.5-50 mu mol/kg) or subplantar (0. 125-0.5 mu mol/paw) administration of L-NAME (but not of its inactive enant iomer, D-NAME) largely reduced the MPO activity in SEE-treated paws. Simila rly, intravenous (200-600 mu mol/kg) or subplantar (2 mu mol/paw) administr ation of aminoguanidine significantly reduced the MPO values of the SEE-inj ected paws. The vasodilator iloprost (0.3 nmol/paw) completely reversed the inhibition by L-NAME or aminoguanidine of the MPO activity in SEE-injected paws. Our results show that the increased vascular permeability and neutro phil accumulation in response to subplantar injection of SEE in the mouse a re inhibited by L-NAME and aminoguanidine by mechanisms probably involving reduction of local microvascular blood Row. (C) 2001 Elsevier Science Inc. All rights reserved.