In vivo transfer of nitric oxide between a plasma protein-bound reservoir and low molecular weight thiols.
Plasma albumin reacts with nitric oxide (NO) to form the bioactive adduct, S-nitroso-albumin (S-NO-albumin). The limited intracellular access of S-NO-albumin suggests the need for a vascular transfer mechanism of NO from a large plasma S-NO-albumin pool to effect biologic function. To study the role of low molecular weight (LMW) thiols in NO transfer in vivo, we administered intravenous S-NO-albumin (1-300 nmol/kg) to rabbits before and after an intravenous infusion of L-cysteine or N-acetyl-L-cysteine. S-NO-albumin produced dose-dependent hypotension that was significantly augmented by prior infusion of either LMW thiol. LMW thiol infusion significantly accelerated the rate of onset and reduced the duration of action of the hypotension induced by S-NO-albumin. The hemodynamic effects of S-NO-albumin after pretreatment with LMW thiols were mimicked by administration of the corresponding LMW S-nitrosothiol. The transfer of NO from albumin to L-cysteine was directly measured in rabbit plasma using a novel technique that couples high performance liquid chromatography to electrochemical detection. These data demonstrate that NO exchange between plasma protein thiol-bound NO and available LMW thiol pools (transnitrosation) occurs in vivo.
Scharfstein
J S
JS
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Keaney
J F
JF
Slivka
A
A
Welch
G N
GN
Vita
J A
JA
Stamler
J S
JS
Loscalzo
J
J
D000111:Acetylcysteine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D008623:Mercaptoethanol; D009569:Nitric Oxide / Q000378:metabolism*; D015538:Nitrosation; D009603:Nitroso Compounds / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011817:Rabbits; D026403:S-Nitrosothiols; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000097:blood / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects
D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; C024940:S-nitroso-N-acetylcysteine; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; C021315:S-nitrosocysteine; D003545:Cysteine; D000111:Acetylcysteine