These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols.
    Author: Kowaluk EA, Fung HL.
    Journal: J Pharmacol Exp Ther; 1990 Dec; 255(3):1256-64. PubMed ID: 2175799.
    Abstract:
    S-nitrosothiols are potent vasodilators in vivo and in vitro, and have recently been proposed as possible endogenous precursors of endothelium-derived nitric oxide (NO). NO release from S-nitrosothiols has generally been assumed to be spontaneous, but this has not been proven. This hypothesis was examined by altering the NO release profiles of two S-nitrosothiols, those of S-nitroso-N-acetylpenicillamine (SNAP) and S-nitroso-glutathione (GSNO), and observing their relaxation potency on isolated endothelium-denuded rat aortic rings. Spontaneous degradation of SNAP and GSNO in tissue bathing medium (monitored by high-performance liquid chromatography) and the associated NO release (assessed by chemiluminescence detection of headspace NO) were enhanced in the presence of 100 microM N-acetylpenicillamine and inhibited in the presence of 100 U/ml superoxide dismutase. However, the relaxant effects of SNAP and GSNO were enhanced in the presence of superoxide dismutase, and diminished in the presence of N-acetylpenicillamine. In addition, the relaxation potencies of SNAP, GSNO, S-nitrosocystein, S-nitroso-N-acetylcysteine and S-nitroso-coenzyme A were not correlated with spontaneous NO generation. These findings therefore argue against spontaneous liberation of NO as a predominant mechanism of S-nitrosothiol action. The highly polar SNAP, GSNO, S-nitrosocysteine and S-nitroso-N-acetylcysteine (octanol, pH 7.4 buffer partition coefficient from less than .025-.052) and the bulky and polar S-nitroso-coenzyme A (MW 797) have similar relaxation potencies, indicating that intracellular penetration of intact S-nitrosothiols may not be required for activity. NO generation from SNAP was examined in subcellular fractions of bovine coronary arterial smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)
    [Abstract] [Full Text] [Related] [New Search]