Effect of aminoguanidine on in vivo expression of cytokines and inducible nitric oxide synthase in the lungs of endotoxemic rats.
Endotoxemia results in the release of multiple mediators such as tumor necrosis factor alpha (TNF-infinity), interleukin-1 beta (IL-1 beta), and nitric oxide (NO), which is thought to be responsible for the hypotension of septic shock. Although there are many reports on the presence of these mediators in serum, in vivo expression of TNF-infinity, IL-1 beta and inducible nitric oxide synthase (iNOS) at the tissue level has not been studied extensively. We investigated in vivo expression of these cytokines and iNOS in the lungs of rats that were injected with saline, endotoxin or endotoxin plus aminoguanidine (AG), an inhibitor of iNOS. Expression of TNF-infinity, IL-1 beta and iNOS was absent in control (saline treated) but was increased in endotoxin treated animals. In animals treated with endotoxin plus AG (400 mg/kg), expression of iNOS was markedly inhibited whereas there was no effect on expression of TNF-infinity and IL-1 beta. The inhibitory effect of AG was probably dose dependent because a lower concentration of AG (50 mg/kg) showed no change in the expression of iNOS.
Joshi
P C
PC
Department of Surgery, University of Mississippi Medical Center, Jackson 39216, USA.
Grogan
J B
JB
Thomae
K R
KR
D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis*; D004731:Endotoxins / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D004731:Endotoxins; D004791:Enzyme Inhibitors; D006146:Guanidines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D009573:Nitrites; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; C004479:pimagedine