A hypothesis on the metabolism of glyceryl trinitrate in vascular endothelial cells

Citation
Yp. Tian et al., A hypothesis on the metabolism of glyceryl trinitrate in vascular endothelial cells, CLIN CHIM A, 313(1-2), 2001, pp. 51-57
Citations number
10
Categorie Soggetti
Medical Research Diagnosis & Treatment
Journal title
CLINICA CHIMICA ACTA
ISSN journal
00098981 → ACNP
Volume
313
Issue
1-2
Year of publication
2001
Pages
51 - 57
Database
ISI
SICI code
0009-8981(200111)313:1-2<51:AHOTMO>2.0.ZU;2-S
Abstract
Background: Extensive research has been conducted regarding the mechanism o f action of glyceryl trinitrate (GTN). It is currently believed that GTN un dergoes a thiol-dependent metabolic pathway and releases its active metabol ite, nitric oxide (NO) and/or S-nitrosothiols (R-SNO). This activates guany lyl cyclase (GC) leading to the formation of cGMP, which is responsible for the relaxation of vascular smooth muscles and the inhibition of platelet a ggregation. The lack of knowledge as to the precise mechanism of GTN action and the modulation of its formation has limited the prevention of toleranc e to GTN. Results: With cultured human vascular endothelial cells (EC), we showed that nitrite was first formed in endothelial cells whose concentrati on was dependent on reduced thiols. Cells preexposed to GTN significantly d ecreased the production of nitrite compared with cells that were not preexp osed. Furthermore, we showed that thiols in cultured cells were oxidized du ring interaction with GTN, which correlated with the time of exposure to GT N. Conclusion: Nitrite is the first active intermediate of GTN metabolism i n endothelial cells. The analysis of the changes of the blood nitrite and r educed thiols concentration is helpful for evaluating the vasodilatation ac tivity of GTN during therapeutic treatments. (C) 2001 Elsevier Science B.V. All rights reserved.