Effect of endotoxin on circulating cyclic GMP in the rat

The aim of this study was to investigate the possible use of plasmatic cyclic GMP as an index of L-arginine/nitric oxide (L-Arg/NO) pathway activation by E. coli endotoxin in vivo. Endotoxin (20 mg kg-1 i.p.) caused a time-dependent increase in plasmatic cyclic GMP in anaesthetised rats which corresponded with the time course of L-Arg/NO pathway activation in aortas from the same rats, but was not prevented by a specific inhibitor of this pathway, NG-nitro-L-arginine methyl ester (1 mg kg-1 or 20 mg kg-1 h-1 i.v.). Elevated plasmatic cyclic GMP was however also associated with an increased plasma concentration of atrial natriuretic peptide (ANP) in endotoxin-treated rats. We conclude that plasma cyclic GMP cannot be used as a direct marker of L-Arg/NO pathway activation by endotoxin but may instead be a reflection of an endotoxin-induced increase in plasma ANP activity.