Thrombin modulates the expression of key regulators of the NO-cGMP pathway in a biphasic manner.

Left panel: Short time stimulation of HUVECs with thrombin (50 nM) increases (A) eNOS and (E) sGC beta 1 expression. Right panel: By contrast, chronic stimulation decreases (B) eNOS and (D) sGC alpha 1 expression, whereas (H) PDE5 expression is increased. At late time points, all effects are concentration-dependent (B, D, H). (I) PDE5 is the only cGMP-hydrolyzing PDE to be upregulated by thrombin (30 nM). Data shown as mean ± SEM (A, C, E, G: n = 3–5/group; B, D, F, H: n = 11/group; I: n = 3/group). *p<0.05, **p<0.01, ***p<0.001 vs cells not exposed to thrombin.