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Figure 5 S 18886 improves endothelial function in patients with coronary artery disease (CAD) treated with aspirin. Endothelium-dependent dilation results from the stimulation of endothelial cells by mechanical factors (e.g., shear stress) and pharmacologic agents (e.g., acetylcholine, bradykinin), which are responsible for the synthesis of endothelial relaxing factors (ERF) and endothelial contracting factors (ECF) by endothelial cells. Releases of ERF and ECF are either aspirin-sensitive (e.g., prostacyclin and thromboxane A₂) or aspirin-insensitive (nitric oxide and isoprostanes). Endothelium-dependent relaxation results from the balance between ERF and ECF production. In normal subjects, ERF production is favored, and endothelial stimulation leads to relaxation. In patients with CAD, endothelial dysfunction results in an imbalance between ERF and ECF production, and impaired peripheral artery dilation is observed, even in patients treated with aspirin. Impaired dilation could be the consequence of an overproduction of aspirin-insensitive ECF, and an underproduction of aspirin-insensitive ERF. S 18886 treatment may partly counterbalance ECF overproduction by blocking TP receptors (TP-R). However, the results of this study cannot exclude partial restoration of ERF production through endothelial TP-R blockade.