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Abstract

In vitro evidence of an endothelial cell-dependent antiplatelet activity for isosorbide dinitrate, but not for its 2- and 5-mononitrate metabolites.

P H Rolland, F P Berenger and J P Cano
Journal of Pharmacology and Experimental Therapeutics January 1987, 240 (1) 234-240;
P H Rolland
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F P Berenger
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J P Cano
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Abstract

In an experimental model in which cultured endothelial cells (EC) and platelets were incubated with autologous plasma, we investigated the pharmacological modulations by isosorbide nitrates (ISN) [isosorbide dinitrate (ISDN) + 2-isosorbide mononitrate (2-ISMN) + 5-ISMN] of the EC-induced inhibition of platelet aggregation; and the associated changes in prostanoid profile of these mixed EC-platelet suspensions. ISDN antiplatelet activities were found to be magnified profoundly by EC, being dependent upon both ISDN concentration and EC number, e.g., 5.10(-5) M ISDN in the presence of 2.10(4) cells, fully arrested ADP-induced aggregation, whereas the same ISDN concentration induced 30% inhibition in control platelet activities. In contrast, there were no significant changes in 2- and 5-ISMN antiaggregating properties, whether incubated in the presence or absence of EC. Thromboxane B2 accumulated noticeably after aggregation, whereas 6-keto-prostaglandin (PG) F1 alpha and PGE2 accumulated poorly in the medium. In the presence of EC, thromboxane B2 accumulation fell in parallel to the extent of aggregation, whereas 6-keto-PGF2 alpha and PGE2 accumulated in the medium. Aspirin-treated, washed ECs still inhibited platelet aggregation. ISDN was the only ISN capable of inducing PG-accumulation profile changes. These results demonstrate the existence of an endothelium-dependent ISDN antiplatelet activity. Furthermore, this effect is specific to ISDN not being shown by its mononitrate metabolites. These results suggest that PG accumulation changes may be a consequence rather than a cause of the inhibition of platelet activity by (ISDN-stimulated) EC.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 240, Issue 1
1 Jan 1987
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Abstract

In vitro evidence of an endothelial cell-dependent antiplatelet activity for isosorbide dinitrate, but not for its 2- and 5-mononitrate metabolites.

P H Rolland, F P Berenger and J P Cano
Journal of Pharmacology and Experimental Therapeutics January 1, 1987, 240 (1) 234-240;

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Abstract

In vitro evidence of an endothelial cell-dependent antiplatelet activity for isosorbide dinitrate, but not for its 2- and 5-mononitrate metabolites.

P H Rolland, F P Berenger and J P Cano
Journal of Pharmacology and Experimental Therapeutics January 1, 1987, 240 (1) 234-240;
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