Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin.

DOI Web Site 被引用文献29件
  • J S Stamler
    Department of Medicine, Harvard University, Cambridge, MA 02138.
  • O Jaraki
    Department of Medicine, Harvard University, Cambridge, MA 02138.
  • J Osborne
    Department of Medicine, Harvard University, Cambridge, MA 02138.
  • D I Simon
    Department of Medicine, Harvard University, Cambridge, MA 02138.
  • J Keaney
    Department of Medicine, Harvard University, Cambridge, MA 02138.
  • J Vita
    Department of Medicine, Harvard University, Cambridge, MA 02138.
  • D Singel
    Department of Medicine, Harvard University, Cambridge, MA 02138.
  • C R Valeri
    Department of Medicine, Harvard University, Cambridge, MA 02138.
  • J Loscalzo
    Department of Medicine, Harvard University, Cambridge, MA 02138.

抄録

<jats:p>We have recently shown that nitric oxide or authentic endothelium-derived relaxing factor generated in a biologic system reacts in the presence of specific protein thiols to form S-nitrosoprotein derivatives that have endothelium-derived relaxing factor-like properties. The single free cysteine of serum albumin, Cys-34, is particularly reactive toward nitrogen oxides (most likely nitrosonium ion) under physiologic conditions, primarily because of its anomalously low pK; given its abundance in plasma, where it accounts for approximately 0.5 mM thiol, we hypothesized that this plasma protein serves as a reservoir for nitric oxide produced by the endothelial cell. To test this hypothesis, we developed a methodology, which involves UV photolytic cleavage of the S--NO bond before reaction with ozone for chemiluminescence detection, with which to measure free nitric oxide, S-nitrosothiols, and S-nitrosoproteins in biologic systems. We found that human plasma contains approximately 7 microM S-nitrosothiols, of which 96% are S-nitrosoproteins, 82% of which is accounted for by S-nitroso-serum albumin. By contrast, plasma levels of free nitric oxide are only in the 3-nM range. In rabbits, plasma S-nitrosothiols are present at approximately 1 microM; 60 min after administration of NG-monomethyl-L-arginine at 50 mg/ml, a selective and potent inhibitor of nitric oxide synthetases, S-nitrosothiols decreased by approximately 40% (greater than 95% of which were accounted for by S-nitrosoproteins, and approximately 80% of which was S-nitroso-serum albumin); this decrease was accompanied by a concomitant increase in mean arterial blood pressure of 22%. These data suggest that naturally produced nitric oxide circulates in plasma primarily complexed in S-nitrosothiol species, principal among which is S-nitroso-serum albumin. This abundant, relatively long-lived adduct likely serves as a reservoir with which plasma levels of highly reactive, short-lived free nitric oxide can be regulated for the maintenance of vascular tone.</jats:p>

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