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Polyaspartoyl.l-arginine inhibits platelet aggregation through stimulation of NO release from endothelial cells.

Authors: Tang, Z  Zhao, M  Li, C  Wang, Y  Peng, S 
Citation: Tang Z, etal., Eur J Pharmacol. 2008 Jun 24;588(1):41-6. Epub 2008 Apr 9.
Pubmed: (View Article at PubMed) PMID:18457831
DOI: Full-text: DOI:10.1016/j.ejphar.2008.04.012

Polyaspartoyl.l-arginine (PDR) is an inhibitor of platelet aggregation ex vivo but in vitro. This study attempts to elucidate the target cell of PDR action and its action mechanism. PDR (1.7-170 microg/ml) significantly inhibited platelet aggregation in vitro in the presence of rat aortic endothelial cells (RAEC), NO synthase inhibitor N-nitro-l-arginine methyl ester (l-NAME) inhibited this effect, but it was ineffective in the RAEC absence. Correspondingly, PDR increased NO level in the supernatants of the platelet reactants in RAEC presence, but failed to influence NO level in RAEC absence, and these effects of PDR were more potent than those of l-arginine. Furthermore, PDR markedly elevated the intracellular level of l-arginine, and it (17-170 microg/ml) also augmented l-citrulline level in RAEC, argininosuccinate lyase (ASL) inhibitor succinate enhanced its effect on l-citrulline but l-NAME weakened it. 170 microg/ml of PDR slightly increased the l-aspartate level in RAEC, and succinate enhanced this effect. However l-arginine, l-aspartate or the combination of l-arginine and l-aspartate failed to change levels of these amino acids. In addition, PDR (170 microg/ml) stimulated the expression of argininosuccinate synthetase (ASS) protein. In conclusion, the endothelial cell is direct target cell of PDR's action; PDR facilitates the entry of l-arginine by serving as a carrier of l-arginine into RAEC; it also supplies aspartic acid and stimulates ASS expression, and then enhances the intracellular citrulline-NO cycle, thus increases the availability of l-arginine and NO synthesis. Therefore the effect of PDR on platelet aggregation is primarily attributed to its stimulation of NO synthesis in endothelial cells; PDR may be a better cardiovascular protective agent than l-arginine.


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CRRD Object Information
CRRD ID: 4140461
Created: 2010-08-30
Species: All species
Last Modified: 2010-08-30
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.