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Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols.
J Pharmacol Exp Ther. 1990 Dec; 255(3):1256-64.JP

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)

Authors+Show Affiliations

Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2175799

Citation

Kowaluk, E A., and H L. Fung. "Spontaneous Liberation of Nitric Oxide Cannot Account for in Vitro Vascular Relaxation By S-nitrosothiols." The Journal of Pharmacology and Experimental Therapeutics, vol. 255, no. 3, 1990, pp. 1256-64.
Kowaluk EA, Fung HL. Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols. J Pharmacol Exp Ther. 1990;255(3):1256-64.
Kowaluk, E. A., & Fung, H. L. (1990). Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols. The Journal of Pharmacology and Experimental Therapeutics, 255(3), 1256-64.
Kowaluk EA, Fung HL. Spontaneous Liberation of Nitric Oxide Cannot Account for in Vitro Vascular Relaxation By S-nitrosothiols. J Pharmacol Exp Ther. 1990;255(3):1256-64. PubMed PMID: 2175799.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols. AU - Kowaluk,E A, AU - Fung,H L, PY - 1990/12/1/pubmed PY - 1990/12/1/medline PY - 1990/12/1/entrez SP - 1256 EP - 64 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 255 IS - 3 N2 - 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) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/2175799/Spontaneous_liberation_of_nitric_oxide_cannot_account_for_in_vitro_vascular_relaxation_by_S_nitrosothiols_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2175799 DB - PRIME DP - Unbound Medicine ER -