Soluble guanylate cyclase (sGC) is a mammalian nitric oxide (NO) sensor. When NO binds to the sGC heme, its GTP cyclase activity markedly increases, thus generating cyclic GMP, which serves to regulate several cell signaling functions[3].On binding of NO to its prosthetic haem group, sGC catalyses the synthesis of the second messenger cyclic guanosine monophosphate (cGMP), which promotes vasodilation and inhibits smooth muscle proliferation, leukocyte recruitment, platelet aggregation and vascular remodelling through a number of downstream mechanisms[4]. Ataciguat (HMR-1766) is a nitric oxide-independent soluble guanylate cyclase (sGC) activator. Ataciguat is able to activate the ferric heme-iron redox form of sGC that stimulate the production of cyclic GMP (cGMP). Ataciguat exhibits vasodilator effects[5].The presence of the endothelium potentiated the relaxation induced by DETA-NO in aortic and coronary rings. In addition, in aortic rings the endothelium potentiated the relaxation induced by ataciguat. In the presence of nitric oxide synthase (NOS) inhibitor, the endothelium effect was abolished to DETA-NO or ataciguat, in both vessels. Ataciguat, 8-Br-cGMP and A23187 were able to induce NO production in HUVECs cells. In the presence of NOS inhibitor, the NO production induced by ataciguat and 8-Br-cGMP was abolished[6].Ataciguat and zaprinast both triggered concentration addicted relaxation on sheep SO rings (p=0.0018, p=0.0025 respectively) but the relaxation of the ataciguat was significantly greater than that of zaprinast at all concentrations (p=0.0024). It was observed that decreased relaxation responses were initiated by ataciguat in the presence of ODQ (p=0.0012)[7].
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