Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Polyaspartoyl.L-arginine enhances prostacyclin synthesis in rat aortic endothelial cells. 1902 30

Endothelium-derived vasodilators, i.e., nitric oxide (NO), prostacyclin (PGI(2)) and prostaglandin E(2) (PGE(2)), play important roles in maintaining cardiovascular homeostasis. C-reactive protein (CRP), a biomarker of inflammation and cardiovascular disease, has been shown to inhibit NO-mediated vasodilation. The goal of this study was to determine whether CRP also affects endothelial arachidonic acid (AA)-prostanoid pathways for vasomotor regulation. Porcine coronary arterioles were isolated and pressurized for vasomotor study, as well as for molecular and biochemical analysis. AA elicited endothelium-dependent vasodilation and PGI(2) release. PGI(2) synthase (PGI(2)-S) inhibitor trans-2-phenyl cyclopropylamine blocked vasodilation to AA but not to serotonin (endothelium-dependent NO-mediated vasodilator). Intraluminal administration of a pathophysiological level of CRP (7 microg/mL, 60 min) attenuated vasodilations to serotonin and AA but not to nitroprusside, exogenous PGI(2), or hydrogen peroxide (endothelium-dependent PGE(2) activator). CRP also reduced basal NO production, caused tyrosine nitration of endothelial PGI(2)-S, and inhibited AA-stimulated PGI(2) release from arterioles. Peroxynitrite scavenger urate failed to restore serotonin dilation, but preserved AA-stimulated PGI(2) release/dilation and prevented PGI(2)-S nitration. NO synthase inhibitor L-NAME and superoxide scavenger TEMPOL also protected AA-induced vasodilation. Collectively, our results suggest that CRP stimulates superoxide production and the subsequent formation of peroxynitrite from basal released NO compromises PGI(2) synthesis, and thus endothelium-dependent PGI(2)-mediated dilation, by inhibiting PGI(2)-S activity through tyrosine nitration. By impairing PGI(2)-S function, and thus PGI(2) release, CRP could promote endothelial dysfunction and participate in the development of coronary artery disease.
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PMID:C-reactive protein impairs coronary arteriolar dilation to prostacyclin synthase activation: role of peroxynitrite. 1945 Jun 4