COMPARISON OF THE EFFECTS OF AMINOGUANIDINE AND N-OMEGA-NITRO-L-ARGININE METHYL-ESTER ON THE MULTIPLE ORGAN DYSFUNCTION CAUSED BY ENDOTOXEMIA IN THE RAT

This study compares the effects of aminoguanidine, a relatively select ive inhibitor of inducible nitric oxide (NO) synthase, and N-omega-nit ro-L-arginine methyl ester (L-NAME), a selective inhibitor of endothel ial NO synthase, on hypotension and multiple organ dysfunction caused by endotoxaemia in the anaesthetised rat. In the sham-operated rats, L -NAME, but not aminoguanidine, caused a dose-dependent increase in blo od pressure. Endotoxin caused hypotension, increases in plasma nitrite (an indicator of inducible NO synthase activity), and dysfunction of kidney, liver and pancreas. Treatment of endotoxic rats with aminoguan idine or L-NAME caused significant and sustained rises in blood pressu re. The increase in plasma nitrite caused by endotoxin was inhibited b y aminoguanidine, but not by L-NAME. Aminoguanidine, but not L-NAME, a ttenuated the renal, liver and pancreatic dysfunction caused by endoto xaemia. Thus, selective inhibition of inducible (aminoguanidine), but not endothelial NO synthase (L-NAME) attenuates the circulatory failur e and the multiple organ failure caused by endotoxaemia.