PMID- 8753795 OWN - NLM STAT- MEDLINE DCOM- 19961010 LR - 20121115 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 225 IP - 2 DP - 1996 Aug 14 TI - Prevention of the expression of inducible nitric oxide synthase by aminoguanidine or aminoethyl-isothiourea in macrophages and in the rat. PG - 525-30 AB - An enhanced formation of nitric oxide (NO) following the induction of the inducible isoform of NOS (iNOS) has been implicated in the pathogenesis of circulatory shock and inflammation. This study elucidates the effects of the NOS inhibitors aminoethyl-isothiourea (AE-ITU), aminoguanidine (AG), NG-methyl-L-arginine (L-NMMA) or N omega-Nitro-L-arginine methyl ester (L-NAME) on the expression of iNOS protein lipopolysaccharide (LPS) in macrophages and the rat (lung homogenates). The expression of iNOS protein was detected by Western blot analysis using a specific iNOS antibody. In the absence of LPS, the iNOS protein was expressed neither in macrophages nor in the lung. LPS (1 microgram.ml-1) resulted in the expression of iNOS protein in macrophages, which was significantly inhibited by pretreatment of cells with AE-ITU or AG, but not by L-NMMA or L-NAME. In addition, LPS (10 mg.kg-1, i.v.) also caused an increase in the expression of iNOS protein in lungs obtained from rats at 6 h after LPS, which was significantly reduced by treatment of LPS-rats with AE-ITU or AG, but not with L-NMMA or L-NAME. Thus, AE-ITU or AG inhibit not only iNOS activity, but also the induction of iNOS protein in vitro and in vivo caused by endotoxin. FAU - Ruetten, H AU - Ruetten H AD - William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, United Kingdom. FAU - Thiemermann, C AU - Thiemermann C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Enzyme Inhibitors) RN - 0 (Guanidines) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - SCQ4EZQ113 (pimagedine) SB - IM MH - Animals MH - Cell Line MH - Enzyme Inhibitors/*pharmacology MH - Guanidines/*pharmacology MH - Lipopolysaccharides/pharmacology MH - Lung/*drug effects/metabolism MH - Macrophages/*drug effects/enzymology MH - Male MH - Mice MH - Nitric Oxide Synthase/*antagonists & inhibitors/genetics MH - Rats MH - Rats, Wistar MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 1996/08/14 00:00 MHDA- 1996/08/14 00:01 CRDT- 1996/08/14 00:00 PHST- 1996/08/14 00:00 [pubmed] PHST- 1996/08/14 00:01 [medline] PHST- 1996/08/14 00:00 [entrez] AID - S0006-291X(96)91206-1 [pii] AID - 10.1006/bbrc.1996.1206 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1996 Aug 14;225(2):525-30. doi: 10.1006/bbrc.1996.1206.