EFFECT OF ENDOTOXEMIA ON PLASMA AND TISSUE-LEVELS OF NITRIC-OXIDE METABOLITES AND GUANIDINO COMPOUNDS

The effect of endotoxemia on the levels of amino acids, nitrates, nitr ites and guanidino compounds it as investigated. Plasma levels of nitr ate and nitrite were significantly increased indicating increased prod uction of nitric oxide during endotoxemia. Plasma concentrations of al anine, glutamine, leucine, methionine, phenylalanine, proline rind mur ine were also significantly elevated. These results indicate that endo toxin produces a hypercatabolic state. The plasma concentration of arg inine was significantly decreased whereas the concentrations of ornith ine and urea, the catabolites of arginine were increased. Decreased pl asma arginine coupled with increased plasma ornithine and urea indicat e that arginine catabolism is increased and arginine synthesis is decr eased during endtoxemia. Plasma levels of creatine, creatinine, guanid ine and guanidinosuccinic acid were significantly elevated whereas hom oarginine levels were significantly decreased. Nitric oxide synthase u tilizes arginine as well as homoarginine as substrates. The decreased concentration of both substrates may be related to alterations in nitr ic oxide synthase activity during endotoxemia. These results suggest t hat in addition to nitric oxide, other catabolites of arginine such as guanidino compounds may be important in the pathophysiology of endoto xemia. Because of the marked increase in guanidinosuccinic acid a know n uremic toxin, we speculate that guanidinosuccinic acid may be import ant in the pathophysiological of endotoxemia.