Comparison of the effects of aminoguanidine and N omega-nitro-L-arginine methyl ester on the multiple organ dysfunction caused by endotoxaemia in the rat.
This study compares the effects of aminoguanidine, a relatively selective inhibitor of inducible nitric oxide (NO) synthase, and N omega-nitro-L-arginine methyl ester (L-NAME), a selective inhibitor of endothelial 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 blood pressure. Endotoxin caused hypotension, increased in plasma nitrite (an indicator of inducible NO synthase activity), and dysfunction of kidney, liver and pancreas. Treatment of endotoxic rats with aminoguanidine or L-NAME caused significant and sustained rises in blood pressure. The increase in plasma nitrite caused by endotoxin was inhibited by aminoguanidine, but not by L-NAME. Aminoguanidine, but not L-NAME, attenuated the renal, liver and pancreatic dysfunction caused by endotoxaemia. Thus, selective inhibition of inducible (aminoguanidine), but not endothelial NO synthase (L-NAME) attenuates the circulatory failure and the multiple organ failure caused by endotoxaemia.
Wu
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William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
Ruetten
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Thiemermann
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000009:adverse effects / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli; D006146:Guanidines / Q000494:pharmacology*; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D004731:Endotoxins; D004791:Enzyme Inhibitors; D006146:Guanidines; D001120:Arginine; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester