Miller, Mark R. and Wadsworth, R.M. (2009) Understanding organic nitrates - a vein hope? British Journal of Pharmacology, 157 (4). pp. 565-567. ISSN 0007-1188Full text not available in this repository. (Request a copy from the Strathclyde author)
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.
|Keywords:||ascorbate deficiency, glyceryl trinitrate, nitric oxide, nitroglycerin, mitochondrial aldehyde dehydrogenase, tolerance, Pharmacy and materia medica, Pharmacology|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Strathprints Administrator|
|Date Deposited:||19 May 2010 15:29|
|Last modified:||02 Sep 2016 02:29|