EFFECT OF AMINOGUANIDINE, A MORE SELECTIVE INHIBITOR FOR INDUCIBLE NITRIC-OXIDE SYNTHASE, ON CARDIOVASCULAR CHANGES IN ENDOTOXIN-SHOCK DOGS

To examine whether aminoguanidine, a putative inhibitor selective for inducible nitric oxide synthase (iNOS), prevents the hemodynamic and b lood gas alterations in endotoxin shock models. Escherichia coli endot oxin was administered (250 ng/kg/min) for 2 hrs in anesthetized dogs w ith or without infusion of aminoguanidine (5 mg/kg/hr) for 2 hrs. Hemo dynamic and blood gas parameters were measured at baseline and 1, 2, 3 , and 4 hrs after endotoxin administration. Infusion of endotoxin resu lted in decrease in MAP and metabolic acidosis. Aminoguanidine prevent ed endotoxin-induced hypotension, while cardiac index, systemic vascul ar resistance, and oxygen delivery remained unchanged. Aminoguanidine alone had no hemodynamic effect on sham-treated animals during 8 hrs p eriod. However, endotoxin-induced metabolic acidosis was not corrected by aminoguanidine. These results demonstrate that aminoguanidine amel iorates endotoxin-induced hypotension by inhibiting nitric oxide (NO) production without any improvement of metabolic acidosis. Possible the rapeutic use of aminoguanidine for endotoxin shock should be cautiousl y considered.