Understanding organic nitrates - a vein hope?

Mark R. Miller, R.M. Wadsworth

Research output: Contribution to journalEditorial

13 Citations (Scopus)

Abstract

The organic nitrate drugs, such as glyceryl trinitrate (GTN; nitroglycerin), are clinically effective in angina because of their dilator profile in veins and arteries. The exact mechanism of intracellular delivery of nitric oxide (NO), or another NO-containing species, from these compounds is not understood. However, mitochondrial aldehyde dehydrogenase (mtALDH) has recently been identified as an organic nitrate bioactivation enzyme. Nitrate tolerance, the loss of effect of organic nitrates over time, is caused by reduced bioactivation and/or generation of NO-scavenging oxygen-free radicals. In a recent issue of the British Journal of Pharmacology, Wenzl et al. show that guinea-pigs, deficient in ascorbate, also have impaired responsiveness to GTN, but nitrate tolerance was not due to ascorbate deficiency that exhibited divergent changes in mtALDH activity. Thus, the complex function of mtALDH appears to be the key to activation of GTN, the active NO species formed and the induction of tolerance that can limit clinical effectiveness of organic nitrate drugs.
Original languageEnglish
Pages (from-to)565-567
Number of pages3
JournalBritish Journal of Pharmacology
Volume157
Issue number4
DOIs
Publication statusPublished - Jun 2009

Fingerprint

Nitrates
Veins
Nitric Oxide
Nitroglycerin
Pharmaceutical Preparations
Free Radicals
Reactive Oxygen Species
Guinea Pigs
Arteries
Pharmacology
Enzymes
Mitochondrial Aldehyde Dehydrogenase

Keywords

  • ascorbate deficiency
  • glyceryl trinitrate
  • nitric oxide
  • nitroglycerin
  • mitochondrial aldehyde dehydrogenase
  • tolerance

Cite this

Miller, Mark R. ; Wadsworth, R.M. / Understanding organic nitrates - a vein hope?. In: British Journal of Pharmacology. 2009 ; Vol. 157, No. 4. pp. 565-567.
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abstract = "The organic nitrate drugs, such as glyceryl trinitrate (GTN; nitroglycerin), are clinically effective in angina because of their dilator profile in veins and arteries. The exact mechanism of intracellular delivery of nitric oxide (NO), or another NO-containing species, from these compounds is not understood. However, mitochondrial aldehyde dehydrogenase (mtALDH) has recently been identified as an organic nitrate bioactivation enzyme. Nitrate tolerance, the loss of effect of organic nitrates over time, is caused by reduced bioactivation and/or generation of NO-scavenging oxygen-free radicals. In a recent issue of the British Journal of Pharmacology, Wenzl et al. show that guinea-pigs, deficient in ascorbate, also have impaired responsiveness to GTN, but nitrate tolerance was not due to ascorbate deficiency that exhibited divergent changes in mtALDH activity. Thus, the complex function of mtALDH appears to be the key to activation of GTN, the active NO species formed and the induction of tolerance that can limit clinical effectiveness of organic nitrate drugs.",
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Understanding organic nitrates - a vein hope? / Miller, Mark R.; Wadsworth, R.M.

In: British Journal of Pharmacology, Vol. 157, No. 4, 06.2009, p. 565-567.

Research output: Contribution to journalEditorial

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AU - Miller, Mark R.

AU - Wadsworth, R.M.

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AB - The organic nitrate drugs, such as glyceryl trinitrate (GTN; nitroglycerin), are clinically effective in angina because of their dilator profile in veins and arteries. The exact mechanism of intracellular delivery of nitric oxide (NO), or another NO-containing species, from these compounds is not understood. However, mitochondrial aldehyde dehydrogenase (mtALDH) has recently been identified as an organic nitrate bioactivation enzyme. Nitrate tolerance, the loss of effect of organic nitrates over time, is caused by reduced bioactivation and/or generation of NO-scavenging oxygen-free radicals. In a recent issue of the British Journal of Pharmacology, Wenzl et al. show that guinea-pigs, deficient in ascorbate, also have impaired responsiveness to GTN, but nitrate tolerance was not due to ascorbate deficiency that exhibited divergent changes in mtALDH activity. Thus, the complex function of mtALDH appears to be the key to activation of GTN, the active NO species formed and the induction of tolerance that can limit clinical effectiveness of organic nitrate drugs.

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KW - nitroglycerin

KW - mitochondrial aldehyde dehydrogenase

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