Glyceryltrinitrate (GTN) is an organic nitrate ester widely used in clinical practice, mainly in the treatment of coronary artery disease. Recently, organic nitrate ester such as GTN have been used in triggering headache, since their vasodilating properties. This effect has been shown to occur as a consequence of the release of nitric oxide (NO), a nitrogen free radical which is endogenously generated by endothelial cells as well as by many other cell types through bioconversion of L-arginine into citrulline by NO synthase (s). In contrast with other NO donors, GTN do not release NO spontaneously being an enzymatic bioconversion required in order endothelial and smooth muscle cells can make NO from exogenous GTN. Indeed, both cultured bovine aorthic endothelial and smooth muscle cells metabolize GTN into NO, a process which seems to occur in microsomes, being the bioconversion of GTN into NO inhibited by sonicating cells as well as by boiling microsomial fraction of cell homogenate. In addition, this site represents the target for organic nitrate ester tolerance, and seems do not interfere with the endogenous L-arginine-NO pathway, since NO synthase inhibitors such as monomethyl-L-arginine (L-NMMA) are unable to antagonize the bioconversion of GTN to NO. In addition, by incubating cells with E. Coli lipopolisaccharide (LPS), a significant elevation of NO formation from exogenous GTN was found, suggesting that an inducible GTN to NO synthase may be responsible for an exaggerated formation of NO when using GTN. This may underlie GTN supersensitivity which may occur in some patients undergoing treatment with organic nitrate ester as well as GTN-triggered headache. In conclusion, vascular endothelial and smooth muscle cells make NO form exogenous GTN by activating an alternative GTN to NO pathway which may represent a novel and potentially useful tool for the understanding of GTN-supersensitivity which may occur in clinical practice.
|Number of pages||5|
|Journal||EOS Rivista di Immunologia ed Immunofarmacologia|
|Publication status||Published - 1998|
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