Effects of aminoguanidine on systemic inflammatory response syndrome induced by platelet activating factor and by lipopolysaccharide in rats.
We investigated the effects of aminoguanidine, a relatively selective inhibitor of inducible nitric oxide (NO) synthase, on the systemic inflammatory response syndrome induced by platelet activating factor (PAF) and by lipopolysaccharide in rats, with emphasis on NO production in vivo. Aminoguanidine treatment improved survival rates after lipopolysaccharide challenge, whereas it aggravated the lethality caused by PAF. Lipopolysaccharide induced a marked increase in the concentrations of nitrate and nitrite in plasma compared with vehicle administration, and the increase was prevented by aminoguanidine. In contrast, PAF challenge with or without aminoguanidine did not affect the concentrations of nitrate and nitrite in plasma compared with vehicle administration. These results suggest that NO derived from inducible NO synthase is not a major participant in the systemic inflammatory response syndrome induced by PAF. Aminoguanidine is not likely to provide beneficial effects in conditions where PAF is produced and the concentrations of nitrate and nitrite in plasma are not significantly increased.
Takano
H
H
First Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Yoshikawa
T
T
Yamaguchi
T
T
Hongo
H
H
Fujii
T
T
Boku
Y
Y
Yoshida
N
N
Yamamoto
H
H
Nakahashi
Y
Y
Yanagisawa
R
R
Kondo
M
M
D000818:Animals; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D009573:Nitrites / Q000097:blood; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology
D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D010972:Platelet Activating Factor; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; C004479:pimagedine