Role of nitric oxide on the increased vascular permeability and neutrophil accumulation 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 microgram/paw) 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 enantiomer N(omega)-nitro-D-arginine methyl ester (D-NAME)], given intravenously (25-100 micromol/kg) or subplantarly (0.25-1.0 micromol/paw), reduced SEB-induced paw oedema significantly. A similar response was observed with aminoguanidine, given either intravenously (200-600 micromol/kg) or subplantarly (2 micromol/paw). In contrast to paw oedema, the plasma exudation in response to SEB 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 iloprost (0.3 nmol/paw). Subplantar injection of SEB (25 microgram/paw) increased by 69% the myeloperoxidase (MPO) activity of SEB-treated paws, indicating the presence of neutrophils. Intravenous (12.5-50 micromol/kg) or subplantar (0.125-0.5 micromol/paw) administration of L-NAME (but not of its inactive enantiomer, D-NAME) largely reduced the MPO activity in SEB-treated paws. Similarly, intravenous (200-600 micromol/kg) or subplantar (2 micromol/paw) administration of aminoguanidine significantly reduced the MPO values of the SEB-injected paws. The vasodilator iloprost (0.3 nmol/paw) completely reversed the inhibition by L-NAME or aminoguanidine of the MPO activity in SEB-injected paws. Our results show that the increased vascular permeability and neutrophil accumulation in response to subplantar injection of SEB in the mouse are inhibited by L-NAME and aminoguanidine by mechanisms probably involving reduction of local microvascular blood flow.
Franco-Penteado
C F
CF
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), PO Box 6111, 13081-970, (SP), Campinas, Brazil.
Desouza
I
I
Teixeira
S A
SA
Ribeiro-DaSilva
G
G
De Nucci
G
G
Antunes
E
E
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D004768:Enterotoxins; D005534:Foot Diseases / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism
D004768:Enterotoxins; D009569:Nitric Oxide; C031818:enterotoxin B, staphylococcal; D009195:Peroxidase; D019001:Nitric Oxide Synthase