INHIBITION OF NITRIC-OXIDE FORMATION DOES NOT AFFECT ENDOTOXIN LETHALITY IN RATS

Endotoxin causes release of nitric oxide (NO) from different types of cells, A causative role has been suggested for NO in endotoxin-induced hypotension, In order to test the hypothesis that NO may be involved in the high mortality rate following endotoxin challenge, the competit ive NO synthase inhibitors N-W nitro-L-arginine methyl ester (L-NAME) and N-G methyl L-arginine (L-NMA), or the NOS substrate L-arginine, we re administered to rats in the presence and absence of endotoxin, Deat h rates were examined after drug injection, Urine nitrite concentratio n and mean arterial blood pressure were examined for 24 h following en dotoxin injection, It was found that endotoxin injection increased mor tality rates, The mortality rate of rats injected with NOS inhibitors or an NOS substrate concomitantly with endotoxin was similar to that o bserved in rats treated with endotoxin alone, Endotoxin elicited a dec rease in mean arterial blood pressure, whereas treatment with NOS inhi bitors prevented this decrease, Treatment with L-arginine markedly exa cerbated the endotoxin effects on blood pressure and resulted in hypot ension 6 h after the endotoxin injection, The urine nitrite concentrat ion increased after injection of endotoxin or L-arginine alone, or aft er injection of endotoxin concomitantly with L-arginine. The urine nit rite concentration after injection of endotoxin together with L-NAME w as smaller than after injection of endotoxin alone, The effects of L-N AME on the urine nitrite concentration and on the blood pressure were reversed with L-arginine, These results do not support the hypothesis that NO mediates the high mortality rates following administration of endotoxin.