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

Abstract：

:Nitric oxide (NO) and prostacyclin (PGI(2)) are two of the most important vasodilators produced by endothelial cells, the regulation of NO on PGI(2) 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 PGI(2) level in RAECs. NO concentration in the medium of RAECs was assessed with fluorometric method; 6-keto-PGF(1 alpha), the stable metabolite of PGI(2), in the medium of RAECs was measured with radioimmunoassay kits; Protein level of PGI(2) synthase in RAECs was determined by Western blot analysis. PDR (17.0 approximately 170 microg/ml, equal to 0.5 microM-5 microM) enhanced NO level in culture medium of RAEC with concentration-dependent manner (P<0.01); L-arginine (170 microg/ml, equal to 1000 microM) and 1.70 microg/ml (0.05 microM) of PDR slightly increased NO level (P>0.05). Interestingly PDR (1.70-500 microg/ml), L-arginine (17.0-170 microg/ml) significantly elevated PGI(2) levels in medium of RAECs (P<0.01), NO synthase inhibitor, N(G)-nitro L-arginine methyl ester (L-NAME), markedly inhibited the elevated PGI(2) levels by PDR and L-arginine. NO donor, sodium nitroprusside(SNP)(1-500 microM), showed the most powerful effects of increasing PGI(2) level in RAECs, which was not influenced by L-NAME. Cyclooxigenase(COX) inhibitor, indomethacin, significantly reduced elevated PGI(2) level by both PDR and SNP in RAEC medium. PDR (170 microg/ml) increased the expression of PGI(2) synthase, L-NAME partly inhibited this effect. In conclusion, PDR enhances PGI(2) synthesis in RAEC, which is attributed to its effect of NO production; the stimulating effect of PDR on PGI(2) synthesis may be mediated via COX and PGI(2) synthase.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Tang Z,Yang J,Liu X,Wang Y,Peng S

doi

10.1016/j.ejphar.2008.11.003

subject

Has Abstract

pub_date

2008-12-28 00:00:00

pages

124-8

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(08)01125-4

journal_volume

601

pub_type

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