New findings in life sciences described from Karl-Franzens ...

Tag : Organic Intermediate

Released : Thursday, October 02, 2008 9:36 PM
2008 OCT 10 - ( NewsRx.com ) -- New investigation results, 'The enigma of nitroglycerinbioactivation and nitrate tolerance: news, views and troubles,' aredetailed in a study published in British Journal of Pharmacology (see also Life Sciences ). "Nitroglycerin (glyceryl trinitrate; GTN) is the most prominentrepresentative of the organic nitrates or nitrovasodilators, aclass of compounds that have been used clinically since the latenineteenth century for the treatment of coronary artery disease(angina pectoris), congestive heart failure and myocardialinfarction. Medline lists more than 15 000 publications on GTN andother organic nitrates, but the mode of action of these drugs isstill largely a mystery," investigators in Graz, Austria report.
"In the first part of this article, we give an overview on themolecular mechanisms of GTN biotransformation resulting in vascularcyclic GMP accumulation and vasodilation with focus on the role ofmitochondrial aldehyde dehydrogenase (ALDH2) and the link betweenthe ALDH2 reaction and activation of vascular soluble guanylatecyclase (sGC). In particular, we address the identity of thebioactive species that activates sGC and the potential involvementof nitrite as an intermediate, describe our recent findingssuggesting that ALDH2 catalyses direct 3-electron reduction of GTNto NO and discuss possible reaction mechanisms. In the second part,we discuss contingent processes leading to markedly reducedsensitivity of blood vessels to GTN, referred to as vascularnitrate tolerance. Again, we focus on ALDH2 and describe thecurrent controversy on the role of ALDH2 inactivation in tolerancedevelopment," wrote B. Mayer and colleagues, Karl-FranzensUniversity.
The researchers concluded: "Finally, we emphasize some of the mostintriguing, in our opinion, unresolved puzzles of GTN pharmacologythat urgently need to be addressed in future studies."
Mayer and colleagues published their study in British Journal of Pharmacology (The enigma of nitroglycerin bioactivation and nitrate tolerance:news, views and troubles. British Journal of Pharmacology , 2008;155(2):170-84).
For additional information, contact B. Mayer,Karl-Franzens-University Graz, Dept. of Pharmacology andToxicology, Graz, Austria.
The publisher of the British Journal of Pharmacology can be contacted at: Nature Publishing Group, Macmillan Building,4 Crinan St., London N1 9XW, England.
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