Nitric oxide (NO.), a
free radical that is generated from
L-arginine by stimulated endothelial cells, neutrophils, activated macrophages, and other cell types, reacts with
superoxide anion (O2.-) to form
peroxynitrite, which itself may be tissue toxic or can then react further to form the highly reactive and toxic
hydroxyl radical (HO.). Because
vascular injury produced by tissue deposition of
immune complexes is linked to formation of toxic products derived from activated neutrophils, we have assessed whether
immune complex-induced injury of rat lung and dermal vasculature is
arginine dependent. The
arginine analogue,
NG-monomethyl-L-arginine (N-MeArg), which blocks NO. formation, protects against
immune complex-induced
vascular injury in rats. The protective effects of N-MeArg are reversed by the presence of
L-arginine but not D-
arginine. Additionally, in the absence of N-MeArg, injury is enhanced by the presence of
L-arginine but not by D-
arginine. Protection by N-MeArg is not associated with diminished recruitment of polymorphonuclear leukocytes. Bronchoalveolar lavage fluids from animals undergoing
immune complex deposition in lung contain the decomposition products of NO.--namely,
nitrite and
nitrate. In the presence of N-MeArg these products are greatly diminished. These data suggest that
immune complex-induced injury of rat lung and skin is
L-arginine dependent. These data also suggest that in vivo metabolic products of
L-arginine, such as NO(.), are directly or indirectly linked to
immune complex-induced tissue injury.