Nitroglycerin metabolism in vascular tissue: Role of glutathione S-transferases and relationship between NO(·) and NO2- formation

M. A. Kurz, Thomas D Boyer, R. Whalen, T. E. Peterson, D. G. Harrison

Research output: Contribution to journalArticle

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Abstract

Nitroglycerin is a commonly employed pharmacological agent which produces vasodilatation by release of nitric oxide (NO(·)). The mechanism by which nitroglycerin releases NO(·) remains undefined. Recently, glutathione S-transferases have been implicated as important contributors to this process. They are known to release NO2- from nitroglycerin, but have not been shown to release NO(·). The present studies were designed to examine the role of endogenous glutathione S-transferases in this metabolic process. Homogenates of dog carotid artery were incubated anaerobically with nitroglycerin, and NO(·) and NO2- production was determined by chemiluminescence. The role of glutathione S-transferases was studied by incubating homogenates with nitroglycerin in the presence of 1 mM GSH or 1 mM S-hexylglutathione, a potent inhibitor of glutathione S-transferases. Homogenates released 163 pmol of NO(·)/h per mg of protein from nitroglycerin, and 2370 pmol of NO2-/h per mg. Adding GSH decreased NO(·) production by 82% and increased NO2- production by 98%. S-Hexylglutathione inhibited glutathione S-transferase activity by 96% and decreased NO2- production by 78%, but had no effect on NO(·) release. A linear relationship between glutathione S-transferase activity and NO2- production was observed, whereas glutathione S-transferase activity and NO(·) release were unrelated. Western-blot analysis demonstrated that dog carotid vascular smooth muscle contained Pi and Mu forms of glutathione S-transferases, with a predominance of the former. Purified preparations of human Pi and rat Mu isoforms metabolized nitroglycerin only to NO2- and not to NO(·). On the basis of these findings, we conclude that (1) glutathione S-transferases do not contribute to the bioconversion of nitroglycerin to NO(·), but instead act as a degradative pathway for nitroglycerin, and (2) the release of NO(·) from nitroglycerin is not dependent on the formation of NO2-.

Original languageEnglish (US)
Pages (from-to)545-550
Number of pages6
JournalBiochemical Journal
Volume292
Issue number2
StatePublished - 1993
Externally publishedYes

Fingerprint

Nitroglycerin
Glutathione Transferase
Metabolism
Blood Vessels
Nitric Oxide
Tissue
Dogs
Bioconversion
Chemiluminescence
Luminescence
Vascular Smooth Muscle
Carotid Arteries
Vasodilation
Muscle
Rats
Protein Isoforms
Western Blotting
Pharmacology

ASJC Scopus subject areas

  • Biochemistry

Cite this

Nitroglycerin metabolism in vascular tissue : Role of glutathione S-transferases and relationship between NO(·) and NO2- formation. / Kurz, M. A.; Boyer, Thomas D; Whalen, R.; Peterson, T. E.; Harrison, D. G.

In: Biochemical Journal, Vol. 292, No. 2, 1993, p. 545-550.

Research output: Contribution to journalArticle

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