cGMP-reducing effects of thrombin in the presence of pharmacological modulators of the nitric oxide-cGMP pathway.

(A) Direct sGC-stimulator BAY 41–2272 (1 µM) und NO donor DETA NONOate (100 µM) elevate cGMP, but the prolonged thrombin challenge (0.3 nM) over 14 hours still reduces cGMP (white bars: controls; grey bars: thrombin). (B) When co-stimulated with DETA NONOate, both (B) Tadalafil and (C) IBMX elevate cGMP; again, however, cGMP-decreasing effects of thrombin were still present under stimulation with these agents. (D) The combination of IBMX and BAY 41–2272 increases cGMP more strongly than either compound alone, but thrombin-induced cGMP reduction is still present. Data shown as mean ± SEM (A: n = 5/group; B: n = 12/group; C: n = 3–5/group; D: n = 5/group). *p<0.05, **p<0.01, ***p<0.001.