Polyaspartoyl·L-arginine enhances prostacyclin synthesis in rat aortic endothelial cells

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Nitric oxide (NO) and prostacyclin (PGI2) are two of the most important vasodilators produced by endothelial cells, the regulation of NO on PGI2 production has not been fully clear yet. Polyaspartoyl·L-arginine (PDR) is an L-arginine residue-rich compound with inhibitory effects of platelet aggregation and thrombosis. This study investigated its effects on NO production in rat aortic endothelial cells (RAECs) and observed the influence of NO on PGI2 level in RAECs. NO concentration in the medium of RAECs was assessed with fluorometric method; 6-keto-PGF1α, the stable metabolite of PGI2, in the medium of RAECs was measured with radioimmunoassay kits; Protein level of PGI2 synthase in RAECs was determined by Western blot analysis. PDR (17.0 ˜ 170 μg/ml, equal to 0.5 μM – 5 μM) enhanced NO level in culture medium of RAEC with concentration-dependent manner (P < 0.01); L-arginine (170 μg/ml, equal to 1000 μM) and 1.70 μg/ml (0.05 μM) of PDR slightly increased NO level (P > 0.05). Interestingly PDR (1.70 – 500 μg/ml), L-arginine (17.0 – 170 μg/ml) significantly elevated PGI2 levels in medium of RAECs (P < 0.01), NO synthase inhibitor, NG-nitro L-arginine methyl ester (L-NAME), markedly inhibited the elevated PGI2 levels by PDR and L-arginine. NO donor, sodium nitroprusside(SNP)(1 – 500 μM), showed the most powerful effects of increasing PGI2 level in RAECs, which was not influenced by L-NAME. Cyclooxigenase(COX) inhibitor, indomethacin, significantly reduced elevated PGI2 level by both PDR and SNP in RAEC medium. PDR (170 μg/ml) increased the expression of PGI2 synthase, L-NAME partly inhibited this effect. In conclusion, PDR enhances PGI2 synthesis in RAEC, which is attributed to its effect of NO production; the stimulating effect of PDR on PGI2 synthesis may be mediated via COX and PGI2 synthase.

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