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The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs.

Strathprints serves world leading Open Access research by the University of Strathclyde, including research by the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), where research centres such as the Industrial Biotechnology Innovation Centre (IBioIC), the Cancer Research UK Formulation Unit, SeaBioTech and the Centre for Biophotonics are based.

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Understanding organic nitrates - a vein hope?

Miller, Mark R. and Wadsworth, R.M. (2009) Understanding organic nitrates - a vein hope? British Journal of Pharmacology, 157 (4). pp. 565-567. ISSN 0007-1188

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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.