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). *ppp(A) 可溶性鸟苷酸环化酶（soluble guanylyl cyclase, sGC）激动剂BAY 41–2272（1 µM）与一氧化氮供体DETA NONOate（100 µM）均可升高环磷酸鸟苷（cyclic guanosine monophosphate, cGMP）水平，但经0.3 nM凝血酶持续刺激14小时后，cGMP水平仍会降低（白色柱形为对照组；灰色柱形为凝血酶处理组）。 (B) 当与DETA NONOate共刺激时，他达拉非（Tadalafil）与3-异丁基-1-甲基黄嘌呤（IBMX）均可升高cGMP水平；但在此两种试剂刺激下，凝血酶的cGMP降低效应仍可观测到。 (D) 联合使用IBMX与BAY 41–2272可较单独使用任一化合物更显著地升高cGMP水平，但凝血酶诱导的cGMP降低效应仍存在。 所有数据以平均值±标准误（standard error of the mean, SEM）表示（A组：n=5/组；B组：n=12/组；C组：n=3~5/组；D组：n=5/组）。*ppp