High doses of
diazepam (10.0-20.0 mg/kg) were shown to reduce the volume of acute inflammatory paw
edema in rats as a response to
carrageenan administration. This effect was attributed to an action of
diazepam on the peripheral-type
benzodiazepine receptor (PBR) present in the adrenal and/or immune/inflammatory cells. The present study was undertaken to analyze the involvement of
nitric oxide (NO) on the effects of
diazepam on
carrageenan-induced paw
edema in rats (
CIPE) and to look for the presence of PBR and inducible/constitutive NO synthases (NOS) on slices taken from the inflamed paws of
diazepam-treated rats. For that, an acute inhibition of NO biosynthesis was achieved using 50.0 mg/kg No mega-nitro-
L-arginine (
L-NAME),
L-arginine (300.0 mg/kg), the true precursor of NO, and D-
arginine (300.0 mg/kg), its false substrate, were also used. The following results were obtained: (1)
diazepam (10.0 and 20.0 mg/kg) decreased
CIPE values in a dose- and time-dependent way; (2)
diazepam effects on
CIPE were increased by
L-NAME pretreatment; (3) treatment with
L-arginine but not with D-
arginine reverted at least in part the decrements of
CIPE values observed after
diazepam administration; (4) PBR were found in endothelial and inflammatory cells that migrated to the inflammatory site at the rat paw; (5) confocal microscopy showed the presence of both PBR and NOS in endothelial and inflammatory cells taken from inflamed paw tissues of rats treated with
diazepam a finding not observed in tissues provided from rats treated with
diazepam's control
solution. These results suggest an important role for NO on the effects of
diazepam on
CIPE. Most probably, these effects reflect a direct action of
diazepam on PBR present in the endothelium of the microvascular ambient and/or on immune/inflammatory cells. An action like that would lead, among other factors, to a decrease in NO, generated by
NO synthase, and thus in the mechanisms responsible for
CIPE.