Thrombin has biphasic effects on cGMP levels in endothelial cells.

(A) Thrombin (30 nM) acutely increases cGMP content in HUVECs; the effects, however, are transient (white bars: controls; grey bars: with thrombin). (B) cGMP elevation by incubation with the NO donor DETA NONOate (100 µM) is partly blunted by thrombin over 14 to 24 hours. (C) Reduction of cGMP levels in DETA NONOate-stimulated cells is concentration-dependent. (D) Thrombin-induced reduction of cGMP levels over 14 hours in DETA NONOate-stimulated cells is completely abolished by direct thrombin inhibitor melagatran (10 µM). Data shown as mean ± SEM (A, B, C: n = 3; D: n = 4/group). *p<0.05, **p<0.01, ***p<0.001 vs cells not exposed to thrombin.