S-nitrosothiol formation in blood of lipopolysaccharide-treated rats.
The administration of the gram-negative bacterial cell wall component lipopolysaccharide (LPS) to experimental animals results in the dramatic up-regulation of the inducible form of nitric oxide synthase (iNOS). The resulting sustained overproduction of nitric oxide (NO) is thought to contribute to the septic shock-like state in these animals. Numerous studies have characterized the kinetics and magnitude of expression of iNOS as well as the production of NO-derived nitrite and nitrate. However, little is known regarding the ability of iNOS-derived NO to interact with physiological substrates such as thiols to yield biologically active S-nitrosothiols during endotoxemia. It has been hypothesized that these relatively stable, vaso-active compounds may serve as a storage system for NO and they may thus play an important role in the pathophysiology associated with endotoxemia. In the present study, we demonstrate that 5 h after i.p. administration of LPS in rats, circulating S-nitrosoalbumin was increased by approximately 3. 4-fold over control. S-nitrosohemoglobin was increased by approximately 25-fold over controls and by threefold over S-nitrosoalbumin. No increase in low molecular weight S-nitrosothiols (i.e., S-nitrosoglutathione and S-nitrosocysteine) could be detected under our experimental conditions. Taken together these data demonstrate that endotoxemia dramatically enhances circulating S-nitrosothiol formation.
Jourd'heuil
D
D
Center for Cardiovascular Sciences, Albany Medical College, Albany, New York 12208, USA.
Gray
L
L
Grisham
M B
MB
D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D006454:Hemoglobins / Q000032:analysis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008623:Mercaptoethanol; D008970:Molecular Weight; D050901:Nitrate Reductase; D009565:Nitrate Reductases / Q000378:metabolism; D009566:Nitrates / Q000097:blood / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood / Q000378:metabolism; D009603:Nitroso Compounds / Q000097:blood* / Q000378:metabolism*; D010108:Oxyhemoglobins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D026422:S-Nitrosoglutathione; D026403:S-Nitrosothiols; D012710:Serum Albumin, Bovine / Q000032:analysis / Q000378:metabolism
D005456:Fluorescent Dyes; D006454:Hemoglobins; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D010108:Oxyhemoglobins; D026403:S-Nitrosothiols; C091665:S-nitrosoalbumin; C103574:S-nitrosohemoglobin; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; C021315:S-nitrosocysteine; D009565:Nitrate Reductases; D050901:Nitrate Reductase; D005978:Glutathione; D003545:Cysteine