[Nitrogen monoxide (NO)- the active principle of organic nitrates]
Feelisch, M. (1993) [Nitrogen monoxide (NO)- the active principle of organic nitrates]. Schweizerische Rundschau für Medizin Praxis , 82, (42), 1167-1171. (PMID:8248688).
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Although organic nitrates have been used in the treatment of patients with angina pectoris for more than 100 years, their mechanism of action was only disclosed during the last years. In the seventies it became already clear that nitrates act via the intracellular messenger cyclic 3,5'-guanosine-monophosphate (cGMP). Later on, S-nitrosothiols were suggested as possible intermediary messengers arising during metabolism of the nitrates. In parallel with the discovery of the endothelium-derived relaxing factor (EDRF) and its biochemical identification as nitric oxide (NO), it became clear that organic nitrates act via the release of NO in the vascular wall and thus by using metabolic pathways identical to those of endogenous EDRF. The target-enzyme for nitrates or for the NO released by them, respectively, thus is the soluble guanylylcyclase. The rate of enzymic stimulation induced by a given nitrate correlates closely with the rate of measured NO production from the nitrate molecule. The highest NO production was detected with nitroglycerin, followed by the group of dinitrates and mononitrates. In the vessel wall both endothelial cells as well as vascular smooth muscle cells can transform nitrates into NO. This might explain, why the antiaggregatory effect of nitrates is more pronounced in the presence of these cells or in vivo than it is in the absence of vascular cells in vitro. In spite of some differences in metabolism, nitrates are thus closely related by their end-product to the endothelium-derived relaxing factor and represent, therefore, an adequate substitution for NO missing in diseased blood vessels.
|Subjects:||Q Science > QD Chemistry
R Medicine > R Medicine (General)
|Divisions:||Faculty of Medicine > Clinical and Experimental Sciences
|Date Deposited:||25 May 2012 14:51|
|Last Modified:||27 Mar 2014 20:21|
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